Mesoionic pesticides

ABSTRACT

Disclosed are compounds of Formula 1, 
     
       
         
         
             
             
         
       
     
     wherein
         X is O or S;   Y is O or S;   and R 1 , R 2 , R 3  and R 4  are as defined in the disclosure.
 
Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention.

FIELD OF THE INVENTION

This invention relates to certain pyrimidinium compounds and theircompositions suitable for agronomic, nonagronomic and animal healthuses, methods of their use for controlling invertebrate pests such asarthropods in both agronomic and nonagronomic environments, and fortreatment of parasite infections in animals or infestations in thegeneral environment.

BACKGROUND OF THE INVENTION

The control of invertebrate pests is extremely important in achievinghigh crop efficiency. Damage by invertebrate pests to growing and storedagronomic crops can cause significant reduction in productivity andthereby result in increased costs to the consumer. The control ofinvertebrate pests in forestry, greenhouse crops, ornamentals, nurserycrops, stored food and fiber products, livestock, household, turf, woodproducts, and public health is also important. Many products arecommercially available for these purposes, but the need continues fornew compounds that are more effective, less costly, less toxic,environmentally safer or have different sites of action.

The control of animal parasites in animal health is essential,especially in the areas of food production and companion animals.Existing methods of treatment and parasite control are being compromiseddue to growing resistance to many current commercial parasiticides. Thediscovery of more effective ways to control animal parasites istherefore imperative.

U.S. Pat. No. 5,151,427 discloses mesoionic pyrimidinium compounds ofFormula i as anthelmintics

wherein, inter alia, R¹ and R² are independently C₁-C₆ alkyl, R³ is aheteroaromatic 6-membered ring, and R⁴ and R⁵ are independently hydrogenor C₁-C₄ alkyl.

The pyrimidinium compounds of the present invention are not disclosed inthis publication.

SUMMARY OF THE INVENTION

This invention is directed to compounds of Formula 1 (including allgeometric and stereoisomers) and compositions containing them and theiruse for controlling invertebrate pests:

wherein

-   -   X is O or S;    -   Y is O or S;    -   R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl,        C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl,        CR²⁴═C(R²⁴)R¹⁰ or C≡CR¹⁰; or    -   R¹ is C₃-C₇ cycloalkyl, C₄-C₈ cycloalkylalkyl or C₅-C₇        cycloalkenyl, each optionally substituted with 1 to 4        substituents independently selected from the group consisting of        halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, 1 cyclopropyl, 1CF₃ and        1OCF₃; or    -   R¹ is phenyl, naphthalenyl or a 5- or 6-membered heteroaromatic        ring, each optionally substituted with 1 to 3 substituents        independently selected from the group consisting of halogen,        cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄        haloalkyl, C₂-C₄ haloalkenyl, C₂-C₄ alkylcarbonyl, C₂-C₄        haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄        alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,        C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹²,        S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆ dialkylamino, SF₅, Si(CH₃)₃,        CHO, hydroxy, OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹; or    -   R¹ is

-   -    or    -   R¹ is C(X¹)R¹⁸, C(═NOR²³)R¹⁸, C(O)NR¹⁶R^(18a),        C(═NNR^(20a)R²³)R¹⁸, C(═NNR^(20a)C(O)R²³)R¹⁸,        C(═NNR^(20a)C(O)OR^(23a))R¹⁸ or C(═NNR^(20a)C(O)NR^(20a)R²³)R¹⁸;        or    -   R¹ is an 8- to 10-membered heteroaromatic bicyclic ring system        optionally substituted on carbon ring members with up to 3        substituents independently selected from the group consisting of        halogen, cyano, nitro, SF₅, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄        alkynyl, C₁-C₄ haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄        haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄        alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,        C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹²,        S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆ dialkylamino, Si(CH₃)₃, CHO,        hydroxy, OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹, and optionally substituted        on nitrogen ring members with methyl; or    -   R¹ is phenyl or a 5- or 6-membered heteroaromatic ring, each        substituted with GQ¹, each optionally substituted with 1Q² and        each optionally substituted with 1 or 2 substituents        independently selected from the group consisting of halogen,        cyano, nitro, SF₅, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl,        C₁-C₄ haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl,        C₂-C₄ alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄        haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄        alkylamino, C₂-C₆ dialkylamino, Si(CH₃)₃, CHO, hydroxy, OC(O)R¹⁹        and N(R²⁰)C(O)R¹⁹; or    -   R¹ is phenyl or a 5- or 6-membered heteroaromatic ring, each        substituted with LQ¹ and optionally substituted with 1 or 2        substituents independently selected from the group consisting of        halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄        alkynyl, C₁-C₄ haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄        haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄        alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,        C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹²,        S(O)₂R¹³, C₁-C₄ alkylamino and C₂-C₆ dialkylamino;    -   each A is independently C(R¹⁶)₂, O, S(O)_(n) or NR¹⁵;    -   each A¹ is independently C(R¹⁷)₂;    -   X¹ is O or S;    -   G is a direct bond, O, S(O)_(n), NH, N(CH₃), CH₂, CH₂O, OCH₂,        C(O), C(O)O, OC(O), C(O)NH or NHC(O);    -   L is a phenyl or 5- or 6-membered heteroaromatic ring optionally        substituted with 1 or 2 substituents independently selected from        the group consisting of halogen, cyano, nitro, C₁-C₄ alkyl,        C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄        alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl,        C₂-C₄ alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl,        C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆        alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄ alkylamino and C₂-C₆        dialkylamino;    -   Q¹ is phenyl or a 5- or 6-membered heteroaromatic ring, each        optionally substituted with 1 to 3 substituents independently        selected from the group consisting of halogen, cyano, nitro,        C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl,        C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄        haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄        alkylamino, C₂-C₆ dialkylamino, SF₅, Si(CH₃)₃, CHO, hydroxy,        OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹;    -   Q² is phenyl or a 5- or 6-membered heteroaromatic ring, each        optionally substituted with 1 or 2 substituents independently        selected from the group consisting of halogen, cyano, nitro,        C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl,        C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄        haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄        alkylamino and C₂-C₆ dialkylamino;    -   R² is C₂-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆        haloalkenyl, C₃-C₆ alkynyl, C₃-C₆ haloalkynyl, CH₂CO₂R²¹,        CR⁵R⁶CH₂OR²¹, CR⁵R⁶CH₂CH₂OR²¹, CR⁵R⁶CH₂S(O)_(n)R²¹ or        CR⁵R⁶CH₂CH₂S(O)_(n)R²¹; or    -   R² is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally        substituted with 1 to 4 substituents selected from the group        consisting of halogen, C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; or    -   R² is CR⁵R⁶Q; or    -   R² is

-   -   R³ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆        haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl or C≡CR¹⁰; or    -   R³ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally        substituted with 1 to 4 substituents independently selected from        the group consisting of halogen, C₁-C₂ alkyl, 1 cyclopropyl and        1CF₃; or    -   R³ is phenyl, naphthalenyl or a 5- or 6-membered heteroaromatic        ring, each optionally substituted with 1 or 2 substituents        independently selected from the group consisting of halogen,        cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄        haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄        haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄        alkylamino and C₂-C₆ dialkylamino;    -   R⁴ is C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆        haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl or C≡CR¹⁰; or    -   R⁴ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally        substituted with 1 to 4 substituents independently selected from        the group consisting of halogen, C₁-C₂ alkyl, 1 cyclopropyl and        1CF₃; or    -   R⁴ is phenyl, naphthalenyl or a 5- or 6-membered heteroaromatic        ring, each optionally substituted with 1 or 2 substituents        independently selected from the group consisting of halogen,        cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄        haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄        haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄        alkylamino and C₂-C₆ dialkylamino; or    -   R³ and R⁴ are taken together with the contiguous linking        nitrogen and carbon atoms to form an optionally substituted ring        R-1

-   -   or ring R-2

-   -   Z is C(R^(8a))═C(R^(8b)), S, O or NCH₃, provided that the        C(R^(8a))═C(R^(8b)) moiety is oriented so the carbon atom bonded        to R^(8b) is connected as R³ in Formula 1;    -   each R⁵ is independently H, F, Cl, cyano or C₁-C₄ alkyl;    -   each R⁶ is independently H, F, C₁ or CH₃;    -   Q is

-   -   Z¹ is O, S or NR¹⁴;    -   each R⁷ is independently H, halogen, cyano, CF₃, C₁-C₃ alkyl or        C₃-C₆ cycloalkyl;    -   R^(8a) is H or F;    -   R^(8b) is H, F, CF₂H or CF₃;    -   each R^(9a) is independently H, halogen, cyano, nitro, C₁-C₄        alkyl, C₁-C₄ haloalkyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄        alkynyl, C₂-C₄ haloalkynyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy,        C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ haloalkoxycarbonyl, C(O)NH₂, C₂-C₄        alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,        C₂-C₄ haloalkylaminocarbonyl, C₃-C₇ halodialkylaminocarbonyl,        SF₅, S(O)_(n)R¹² or S(O)₂R¹³; or C₃-C₆ cycloalkyl or C₄-C₇        cycloalkylalkyl, each optionally substituted with 1 to 4        substituents selected from the group consisting of halogen,        C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; or phenyl or a 5- or        6-membered heteroaromatic ring, each optionally substituted with        1 or 2 substituents independently selected from the group        consisting of halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl,        C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄        haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄        alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,        C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹²,        S(O)₂R¹³, C₁-C₄ alkylamino and C₂-C₆ dialkylamino;    -   each R^(9b) is independently H, halogen, cyano, C₁-C₄ alkyl,        C₁-C₄ haloalkyl, C₁-C₄ alkoxy or C₁-C₄ haloalkoxy; or phenyl or        pyridinyl, each optionally substituted with 1 or 2 substituents        independently selected from the group consisting of halogen,        cyano, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₄ alkoxy, C₁-C₄        haloalkoxy, S(O)_(n)R¹² and S(O)₂R¹³;    -   each R¹⁰ is independently Si(R¹¹)₃; or phenyl or pyridinyl, each        optionally substituted with 1 to 3 substituents independently        selected from the group consisting of halogen, cyano, nitro,        SF₅, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl,        C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₂-C₆ alkoxyalkyl, C₁-C₄        alkoxy, C₁-C₄ haloalkoxy, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄        alkylamino and C₂-C₆ dialkylamino;    -   each R¹¹ is independently C₁-C₄ alkyl;    -   each R¹² is independently C₁-C₄ alkyl or C₁-C₄ haloalkyl;    -   each R¹³ is independently C₁-C₄ alkylamino, C₂-C₆ dialkylamino        or —NCH₂Z²CH₂;    -   R¹⁴ is H, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₂-C₅ alkoxycarbonyl,        C₂-C₅ alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl,        C(O)NCH₂Z²CH₂, S(O)_(n)R¹² or S(O)₂R¹³; or phenyl or        pyridinyl, each optionally substituted with 1 to 3 substituents        independently selected from the group consisting of halogen,        cyano, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, S(O)_(n)R¹²        and S(O)₂R¹³;    -   each R¹⁵ is independently C₁-C₄ alkyl;    -   each R¹⁶ is independently H or C₁-C₄ alkyl;    -   each R¹⁷ is independently H, F or CH₃;    -   R¹⁸ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl, C₁-C₆        alkoxy, C₁-C₆ alkylamino or C₂-C₇ dialkylamino; or phenyl or a        5- or 6-membered heteroaromatic ring, each optionally        substituted with 1 to 3 substituents independently selected from        the group consisting of halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy,        C₁-C₄ haloalkoxy, S(O)_(n)R¹² and S(O)₂R¹³;    -   R^(18a) is phenyl or a 5- or 6-membered heteroaromatic ring,        each optionally substituted with 1 to 3 substituents        independently selected from the group consisting of halogen,        C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, S(O)_(n)R¹² and        S(O)₂R¹³;    -   each R¹⁹ is independently C₁-C₄ alkyl;    -   each R²⁰ is independently H or C₁-C₄ alkyl;    -   each R^(20a) is independently C₁-C₄ alkyl;    -   each R²¹ is independently H or C₁-C₄ alkyl;    -   R²³ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆        haloalkenyl, C₃-C₆ alkynyl, C₃-C₆ haloalkynyl or CH₂CO₂R²¹; or    -   R²³ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each        optionally substituted with 1 to 4 substituents independently        selected from the group consisting of halogen, C₁-C₂ alkyl, 1        cyclopropyl and 1CF₃; or    -   R²³ is phenyl or a 5- or 6-membered heteroaromatic ring, each        optionally substituted with 1 to 3 substituents independently        selected from the group consisting of halogen, cyano, nitro,        C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl,        C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄        haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄        alkylamino and C₂-C₆ dialkylamino;    -   R^(23a) is C₁-C₆ alkyl, C₂-C₆ haloalkyl, C₃-C₆ alkenyl or C₃-C₆        cycloalkyl;    -   each R²⁴ is independently H, F or CH₃;    -   m is 0, 1, 2 or 3;    -   each n is independently 0, 1 or 2;    -   p is 0, 1, 2, 3 or 4;    -   each q is independently 0, 1 or 2;    -   y is 1 or 2; and    -   each Z² is independently CH₂CH₂, CH₂CH₂CH₂ or CH₂OCH₂.

This invention is also directed to such compounds of Formula 1(including all geometric and stereoisomers) and compositions containingthem and their use for controlling invertebrate pests as describedabove, and further herein, provided that (a) when R² is CH₂CH═CH₂, R³and R⁴ are taken together to form ring R-2, Z is CH═CH, X is O and Y isO, then R¹ is other than H, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH═CH₂ orunsubstituted phenyl; (b) when R¹ is H, R³ and R⁴ are taken together toform ring R-2, Z is CH═CH, X is O and Y is O, then R² is other thanCH₂CH═CH₂ or CH₂C≡CH; (c) when R¹ is CH₂CH₃, R³ and R⁴ are takentogether to form ring R-2, Z is CH═CH, X is O and Y is O, then R² isother than CH₂(CH₂)₃CH₃; (d) when R³ is H, R² and R⁴ are bothcyclohexyl, X is O and Y is O, then R¹ is other than CH₃; (e) when R¹ isH or C₁-C₃ n-alkyl, R³ and R⁴ are taken together to form ring R-2, Z isS, X is O and Y is O, then R² is other than C₁-C₆ alkyl or C₃-C₄alkoxyalkyl; (f) when R² is cyclopropylmethyl, R³ and R⁴ are takentogether to form ring R-2, Z is S, X is O and Y is O, then R¹ is otherthan CH₃, CH₂CH₃ or CH₂CH₂CH₃; (g) when R¹ is unsubstituted phenyl, R³and R⁴ are taken together to form ring R-2, Z is S, X is O and Y is O,then R² is other than C₃-C₄ alkoxyalkyl; and (h) when R¹ is Br, R³ andR⁴ are taken together to form ring R-2, Z is S, X is O and Y is O, thenR² is other than CH₂CH₃.

This invention also provides a composition comprising a compound ofFormula 1 and at least one additional component selected from the groupconsisting of surfactants, solid diluents and liquid diluents. In oneembodiment, this invention also provides a composition for controllingan invertebrate pest comprising a compound of Formula 1 (i.e. in abiologically effective amount) and at least one additional componentselected from the group consisting of surfactants, solid diluents andliquid diluents, said composition optionally further comprising at leastone additional biologically active compound or agent (i.e. in abiologically effective amount).

This invention further provides a composition for protecting an animalfrom an invertebrate parasitic pest comprising a parasiticidallyeffective amount of a compound of Formula 1 (i.e. in a parasiticidallyeffective amount) and at least one carrier.

This invention further provides a spray composition for controlling aninvertebrate pest comprising a compound of Formula 1 or the compositionsdescribed above (i.e. in a biologically effective amount), and apropellant. This invention also provides a bait composition forcontrolling an invertebrate pest comprising a compound of Formula 1 orthe compositions described in the embodiments above (i.e. in abiologically effective amount), one or more food materials, optionallyan attractant, and optionally a humectant.

This invention further provides a trap device for controlling aninvertebrate pest comprising said bait composition and a housing adaptedto receive said bait composition, wherein the housing has at least oneopening sized to permit the invertebrate pest to pass through theopening so the invertebrate pest can gain access to said baitcomposition from a location outside the housing, and wherein the housingis further adapted to be placed in or near a locus of potential or knownactivity for the invertebrate pest.

This invention provides a method for controlling an invertebrate pestcomprising contacting the invertebrate pest or its environment with abiologically effective amount of a compound of Formula 1 (e.g., as acomposition described herein). This invention also relates to suchmethod wherein the invertebrate pest or its environment is contactedwith a composition comprising a biologically effective amount of acompound of Formula 1 and at least one additional component selectedfrom the group consisting of surfactants, solid diluents and liquiddiluents, said composition optionally further comprising a biologicallyeffective amount of at least one additional biologically active compoundor agent.

This invention also provides a method for protecting a seed from aninvertebrate pest comprising contacting the seed with a biologicallyeffective amount of a compound of Formula 1 (e.g., as a compositiondescribed herein). This invention also relates to the treated seed.

This invention further provides a method for treating, preventing,inhibiting and/or killing ecto and/or endoparasites comprisingadministering to and/or on the animal a parasiticidally effective amountof a compound of Formula 1 (e.g., as a composition described herein).This invention also relates to such method wherein a parasiticidallyeffective amount of a compound of Formula 1 (e.g., as a compositiondescribed herein) is administered to the environment (e.g., a stall orblanket) in which an animal resides.

DETAILS OF THE INVENTION

As used herein, the terms “comprises,” “comprising,” “includes,”“including,” “has,” “having,” “contains” or “containing,” or any othervariation thereof, are intended to cover a non-exclusive inclusion. Forexample, a composition, a mixture, process, method, article, orapparatus that comprises a list of elements is not necessarily limitedto only those elements but may include other elements not expresslylisted or inherent to such composition, mixture, process, method,article, or apparatus. Further, unless expressly stated to the contrary,“or” refers to an inclusive or and not to an exclusive or. For example,a condition A or B is satisfied by any one of the following: A is true(or present) and B is false (or not present), A is false (or notpresent) and B is true (or present), and both A and B are true (orpresent).

Also, the indefinite articles “a” and “an” preceding an element orcomponent of the invention are intended to be nonrestrictive regardingthe number of instances (i.e. occurrences) of the element or component.Therefore “a” or “an” should be read to include one or at least one, andthe singular word form of the element or component also includes theplural unless the number is obviously meant to be singular.

As referred to in this disclosure, the term “invertebrate pest” includesarthropods, gastropods and nematodes of economic importance as pests.The term “arthropod” includes insects, mites, spiders, scorpions,centipedes, millipedes, pill bugs and symphylans. The term “gastropod”includes snails, slugs and other Stylommatophora. The term “nematode”includes all of the helminths, such as: roundworms, heartworms, andphytophagous nematodes (Nematoda), flukes (Tematoda), Acanthocephala,and tapeworms (Cestoda).

In the context of this disclosure “invertebrate pest control” meansinhibition of invertebrate pest development (including mortality,feeding reduction, and/or mating disruption), and related expressionsare defined analogously.

The term “agronomic” refers to the production of field crops such as forfood and fiber and includes the growth of corn, soybeans and otherlegumes, rice, cereal (e.g., wheat, oats, barley, rye, rice, maize),leafy vegetables (e.g., lettuce, cabbage, and other cole crops),fruiting vegetables (e.g., tomatoes, pepper, eggplant, crucifers andcucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g.,pome, stone and citrus), small fruit (berries, cherries) and otherspecialty crops (e.g., canola, sunflower, olives).

The term “nonagronomic” refers to other than field crops, such ashorticultural crops (e.g., greenhouse, nursery or ornamental plants notgrown in a field), residential, agricultural, commercial and industrialstructures, turf (e.g., sod farm, pasture, golf course, lawn, sportsfield, etc.), wood products, stored product, agro-forestry andvegetation management, public health (i.e. human) and animal health(e.g., domesticated animals such as pets, livestock and poultry,undomesticated animals such as wildlife) applications.

Nonagronomic applications include protecting an animal from aninvertebrate parasitic pest by administering a parasiticidally effective(i.e. biologically effective) amount of a compound of the invention,typically in the form of a composition formulated for veterinary use, tothe animal to be protected. As referred to in the present disclosure andclaims, the terms “parasiticidal” and “parasiticidally” refers toobservable effects on an invertebrate parasite pest to provideprotection of an animal from the pest. Parasiticidal effects typicallyrelate to diminishing the occurrence or activity of the targetinvertebrate parasitic pest. Such effects on the pest include necrosis,death, retarded growth, diminished mobility or lessened ability toremain on or in the host animal, reduced feeding and inhibition ofreproduction. These effects on invertebrate parasite pests providecontrol (including prevention, reduction or elimination) of parasiticinfestation or infection of the animal.

In the above recitations, the term “alkyl”, used either alone or incompound words such as “haloalkyl” includes straight-chain or branchedalkyl, such as, methyl, ethyl, n-propyl, i-propyl, or the differentbutyl, pentyl or hexyl isomers. “Alkenyl” includes straight-chain orbranched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and thedifferent butenyl, pentenyl and hexenyl isomers. “Alkenyl” also includespolyenes such as 1,2-propadienyl and 2,4-hexadienyl. “Alkynyl” includesstraight-chain or branched alkynes such as ethynyl, 1-propynyl,2-propynyl and the different butynyl, pentynyl and hexynyl isomers.“Alkynyl” can also include moieties comprised of multiple triple bondssuch as 2,5-hexadiynyl.

“Alkoxy” includes, for example, methoxy, ethoxy, n-propyloxy,isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers.“Alkoxyalkyl” denotes alkoxy substitution on alkyl. Examples of“alkoxyalkyl” include CH₂OCH₃, CH₂CH₂OCH₃, CH₂OCH₂CH₃, CH₂OCH₂CH₂CH₂CH₃and CH₂CH₂OCH₂CH₃.

“Cycloalkyl” includes, for example, cyclopropyl, cyclobutyl, cyclopentyland cyclohexyl. The term “cycloalkylalkyl” denotes cycloalkylsubstitution on an alkyl moiety. Examples of “cycloalkylalkyl” includecyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moietiesbonded to straight-chain or branched alkyl groups.

The term “halogen”, either alone or in compound words such as“haloalkyl”, or when used in descriptions such as “alkyl substitutedwith halogen” includes fluorine, chlorine, bromine or iodine. Further,when used in compound words such as “haloalkyl”, or when used indescriptions such as “alkyl substituted with halogen” said alkyl may bepartially or fully substituted with halogen atoms which may be the sameor different. Examples of “haloalkyl” or “alkyl substituted withhalogen” include CF₃, CH₂Cl, CH₂CF₃ and CCl₂CF₃. The terms “haloalkoxy”,“haloalkenyl”, “haloalkynyl”, and the like, are defined analogously tothe term “haloalkyl”. Examples of “haloalkoxy” include OCF₃, OCH₂CCl₃,OCH₂CH₂CHF₂ and OCH₂CF₃. Examples of “haloalkenyl” include CH₂CH═C(Cl)₂and CH₂CH═CHCH₂CF₃. Examples of “haloalkynyl” include CHClC≡CH, C≡CCF₃,C≡CCl₃ and CH₂C≡CCH₂F.

“Alkylamino” denotes an NH radical substituted with straight-chain orbranched alkyl. Examples of “alkylamino” include NHCH₂CH₃, NHCH₂CH₂CH₃,and NHCH₂CH(CH₃)₂. “Dialkylamino” denotes an N radical substitutedindependently with two straight-chain or branched alkyl groups. Examplesof “dialkylamino” include N(CH₃)₂, N(CH₃CH₂CH₂)₂ and N(CH₃)CH₂CH₃.“Halodialkylamino” denotes one straight-chain or branched alkyl moietyand one straight-chain or branched haloalkyl moiety bonded to an Nradical, or two independent straight-chain or branched haloalkylmoieties bonded to an N radical, wherein “haloalkyl” is as definedabove. Examples of “halodialkylamino” include N(CH₂CH₃)(CH₂CH₂Cl) andN(CF₂CF₃)₂.

“Alkylcarbonyl” denotes a straight-chain or branched alkyl moiety bondedto a C(O) moiety. The chemical abbreviations C(O) and C(═O) as usedherein represent a carbonyl moiety. Examples of “alkylcarbonyl” includeC(O)CH₃, C(O)CH₂CH₂CH₃ and C(O)CH(CH₃)₂. Examples of “haloalkylcarbonyl”include C(O)CF₃, C(O)CCl₃, C(O)CH₂CF₃ and C(O)CF₂CF₃.

“Alkoxycarbonyl” denotes a straight-chain or branched alkyl moietybonded to a CO₂ moiety. The chemical abbreviations CO₂ and C(O)O as usedherein represent an ester moiety. Examples of “alkoxycarbonyl” includeC(O)OCH₃, C(O)CH₂CH₃, C(O)OCH₂CH₂CH₃ and C(O)OCH(CH₃)₂.

“Alkylaminocarbonyl” denotes a straight-chain or branched alkyl moietybonded to a C(O)NH moiety. The chemical abbreviations C(O)NH, and C(O)Nas used herein represent an amide moiety (i.e. an aminocarbonyl group).Examples of “alkylaminocarbonyl” include C(O)NHCH₃, C(O)NHCH₂CH₂CH₃ andC(O)NHCH(CH₃)₂. “Dialkylaminocarbonyl” denotes two independentstraight-chain or branched alkyl moieties bonded to a C(O)N moiety.Examples of “dialkylaminocarbonyl” include C(O)N(CH₃)₂ andC(O)N(CH₃)(CH₂CH₃).

The chemical abbreviation C(O)NCH₂Z²CH₂ as used herein represents adialkylaminocarbonyl moiety wherein the two alkyl groups are connectedto form a ring as shown below.

The chemical abbreviation NCH₂Z²CH₂ is defined analogously.

The chemical abbreviation C(═NOR²³)R¹⁸ as used herein represents bothgeometric isomers of the oxime moiety as shown below.

When R³ and R⁴ are taken together with the contiguous linking nitrogenand carbon atoms to form an optionally substituted ring R-2 and Z isC(R^(8a))═C(R^(8b)), the C(R^(8a))═C(R^(8b)) moiety is oriented so thecarbon atom bonded to R^(8b) is connected as R³ in Formula 1 as shownbelow.

The wavy line in the above structures and elsewhere in the disclosure(e.g., X-24 through X-128 and Y-30 through Y-71 preceding Table 1)indicates the attachment position of the molecular fragment to theremainder of the molecule.

The total number of carbon atoms in a substituent group is indicated bythe “C_(i)-C_(j)” prefix where i and j are numbers from 1 to 7. Forexample, C₁-C₄ alkyl designates methyl through butyl; C₂ alkoxyalkyldesignates CH₂OCH₃; C₃ alkoxyalkyl designates, for example, CH₃CH(OCH₃),CH₂CH₂OCH₃ or CH₂OCH₂CH₃; and C₄ alkoxyalkyl designates the variousisomers of an alkyl group substituted with an alkoxy group containing atotal of four carbon atoms, examples including CH₂OCH₂CH₂CH₃ andCH₂CH₂OCH₂CH₃.

When a compound is substituted with a substituent bearing a subscriptthat indicates the number of said substituents can exceed 1, saidsubstituents (when they exceed 1) are independently selected from thegroup of defined substituents, e.g., (R⁷)_(p), p is 0, 1, 2, 3 or 4.When a group contains a substituent which can be hydrogen, for exampleR¹ or R³, then when this substituent is taken as hydrogen, it isrecognized that this is equivalent to said group being unsubstituted.When a variable group is shown to be optionally attached to a position,for example (R^(v))_(r) in U-36 of Exhibit 1 wherein r may be 0, thenhydrogen can be at the position even if not recited in the variablegroup definition. When one or more positions on a group are said to be“not substituted” or “unsubstituted”, then hydrogen atoms are attachedto take up any free valency.

The term “heteroaromatic ring” denotes an aromatic ring in which atleast one atom forming the ring backbone is not carbon, e.g., nitrogen,oxygen or sulfur. Typically a heteroaromatic ring contains no more than4 nitrogens, no more than 1 oxygen and no more than 1 sulfur. Unlessotherwise indicated, heteroaromatic rings can be attached through anyavailable carbon or nitrogen by replacement of a hydrogen on said carbonor nitrogen. “Aromatic” indicates that each of the ring atoms isessentially in the same plane and has a p-orbital perpendicular to thering plane, and in which (4n+2)π electrons, where n is a positiveinteger, are associated with the ring to comply with Hückel's rule. Theterm “heteroaromatic bicyclic ring system” denotes a ring systemconsisting of two fused rings, in which at least one of the two rings isa heteroaromatic ring as defined above.

When a radical (e.g., cycloalkyl in the definition of R¹) is optionallysubstituted with listed substituents with the number of substituentsstated (e.g., “1 to 4”), then the radical may be unsubstituted orsubstituted with a number of substituents ranging up to the high numberstated (e.g., “4”), and the attached substituents are independentlyselected from the substituents listed. When the substituent listincludes a lower limit for a particular substituent (e.g., “1cyclopropyl”), this accordingly restricts number of instances of thatparticular substituent among the substituents attached to the radical.Thus in regards to R¹, while up to four substituents may be attached tothe cycloalkyl radical, only one of the substituents may be cyclopropyl.

When a substituent (e.g., R¹) is a 5- or 6-membered nitrogen-containingheteroaromatic ring, it can be attached to the remainder of Formula 1though any available carbon or nitrogen ring atom, unless otherwisedescribed. As noted above, substituents such as R¹ can be (among others)phenyl optionally substituted with one to three substituents selectedfrom a group of substituents as defined in the Summary of the Invention.An example of phenyl optionally substituted with one to threesubstituents is the ring illustrated as U-1 in Exhibit 1, wherein R^(v)is as defined in the Summary of the Invention (e.g., for R¹) and r is aninteger from 0 to 3.

As noted above, substituents such as R¹ can be (among others) a 5- or6-membered heteroaromatic ring, optionally substituted with one or moresubstituents selected from a group of substituents as defined in theSummary of Invention. Examples of a 5- or 6-membered heteroaromatic ringoptionally substituted with one or more substituents include the ringsU-2 through U-61 illustrated in Exhibit 1 wherein R^(v) is anysubstituent as defined in the Summary of the Invention (e.g., for R¹)and r is an integer from 0 to 2, limited by the number of availablepositions on each U group. As U-29, U-30, U-36, U-37, U-38, U-39, U-40,U-41, U-42 and U-43 have only one available position, for these U groupsr is limited to the integers 0 or 1, and r being 0 means that the Ugroup is unsubstituted and a hydrogen is present at the positionindicated by (R^(v))_(r).

Exhibit 1

As noted above, substituents such as R¹ can be (among others) an 8-, 9-or 10-membered heteroaromatic bicyclic ring system optionallysubstituted with up to 3 substituents selected from a group ofsubstituents as defined in the Summary of Invention. Examples of a 8-,9- or 10-membered heteroaromatic bicyclic ring system optionallysubstituted with up to 3 substituents include the ring systems H-1through H-23 illustrated in Exhibit 2 wherein R^(v) is any substituentas defined in the Summary of the Invention (e.g., halogen, cyano, nitro,SF₅, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆dialkylamino on carbon ring members and methyl on nitrogen ring members)and r is an integer from 0 to 3, limited by the number of availablepositions on each H group.

Exhibit 2

Although R^(v) groups are shown in the structures U-1 through U-61 andH-1 through H-23, it is noted that they do not need to be present sincethey are optional substituents. The nitrogen atoms that requiresubstitution to fill their valence are substituted with H or R^(v). Notethat when the attachment point between (R^(v))_(r) and the U or H groupis illustrated as floating, (R^(v))_(r) can be attached to any availablecarbon atom or nitrogen atom of the U or H group. Note that when theattachment point on the U or H group is illustrated as floating, the Uor H group can be attached to the remainder of Formula 1 through anyavailable carbon or nitrogen of the U or H group by replacement of ahydrogen atom. Note that some U groups can only be substituted with lessthan 2 R^(v) groups (e.g., U-2 through U-5, U-7 through U-48, and U-52through U-61).

A wide variety of synthetic methods are known in the art to enablepreparation of aromatic and nonaromatic heterocyclic rings and ringsystems; for extensive reviews see the eight volume set of ComprehensiveHeterocyclic Chemistry, A. R. Katritzky and C. W. Rees editors-in-chief,Pergamon Press, Oxford, 1984 and the twelve volume set of ComprehensiveHeterocyclic Chemistry II, A. R. Katritzky, C. W. Rees and E. F. V.Scriven editors-in-chief, Pergamon Press, Oxford, 1996.

The compounds of Formula 1 are mesoionic inner salts. “Inner salts”,also known in the art as “zwitterions”, are electrically neutralmolecules but carry formal positive and negative charges on differentatoms in each valence bond structure according to valence bond theory.Furthermore the molecular structure of the compounds of Formula 1 can berepresented by the six valence bond structures shown below, each placingthe formal positive and negative charges on different atoms. Because ofthis resonance, the compounds of Formula 1 are also described as“mesoionic”. Although for sake of simplicity, the molecular structure ofFormula 1 is depicted as a single valence bond structure in the presentdisclosure and claims, this particular valence bond structure is to beunderstood as representative of all six valence bond structures relevantto bonding in molecules of compounds of Formula 1. Therefore referenceto Formula 1 in the present disclosure and claims relates to all sixapplicable valence bond structures and other (e.g., molecular orbitaltheory) structures unless otherwise specified.

Compounds of this invention can exist as one or more stereoisomers. Thevarious stereoisomers include enantiomers, diastereomers, atropisomersand geometric isomers. For example, substituents and other molecularconstituents such as R¹ may contain chiral centers. One skilled in theart will appreciate that one stereoisomer may be more active and/or mayexhibit beneficial effects when enriched relative to the otherstereoisomer(s) or when separated from the other stereoisomer(s).Additionally, the skilled artisan knows how to separate, enrich, and/orto selectively prepare said stereoisomers. This invention comprisesracemic mixtures as well as enriched and essentially purestereoconfigurations at these chiral centers.

Compounds of this invention can exist as one or more conformationalisomers due to restricted bond rotation caused by steric hinderance. Forexample, a compound of Formula 1 wherein R¹ is phenyl substituted in theortho-position with a sterically demanding alkyl group (e.g., isopropyl)may exist as two rotamers due to restricted rotation about theR¹-pyrimidinium ring bond. This invention comprises mixtures ofconformational isomers. In addition, this invention includes compoundsthat are enriched in one conformer relative to others.

Compounds of Formula 1 can exist in the solid phase as polymorphs (i.e.different crystalline forms). The term “polymorph” refers to aparticular crystalline form of a chemical compound that can crystallizein different crystalline forms, these forms having differentarrangements and/or conformations of the molecules in the crystallattice. Although polymorphs can have the same chemical composition,they can also differ in composition due the presence or absence ofco-crystallized water or other molecules, which can be weakly orstrongly bound in the lattice. Polymorphs can differ in such chemical,physical and biological properties as crystal shape, density, hardness,color, chemical stability, melting point, hygroscopicity,suspensibility, dissolution rate and biological availability. Oneskilled in the art will appreciate that a polymorph of a compound ofFormula 1 can exhibit beneficial effects (e.g., suitability forpreparation of useful formulations) relative to another polymorph or amixture of polymorphs of the same compound of Formula 1. Preparation andisolation of a particular polymorph of a compound of Formula 1 can beachieved by methods known to those skilled in the art including, forexample, crystallization using selected solvents and temperatures. Thisinvention comprises both individual polymorphs and mixtures ofpolymorphs, including mixtures enriched in one polymorph relative toothers.

Embodiments of the present invention as described in the Summary of theInvention include those described below. In the following Embodimentsreference to “a compound of Formula 1” includes the definitions ofsubstituents specified in the Summary of the Invention unless furtherdefined in the Embodiments. The compounds of Formulae 1r and is arevarious subsets of Formula 1.

-   -   Embodiment 1. A compound of Formula 1 wherein X is O.    -   Embodiment 2. A compound of Formula 1 wherein X is S.    -   Embodiment 3. A compound of Formula 1 or Embodiments 1 or 2        wherein Y is O.    -   Embodiment 4. A compound of Formula 1 or Embodiments 1 or 2        wherein Y is S.    -   Embodiment 5. A compound of Formula 1 or any of Embodiments 1-4        wherein R¹ is H or halogen.    -   Embodiment 6. A compound of Formula 1 or any of Embodiments 1-4        wherein R¹ is phenyl or a 6-membered heteroaromatic ring, each        optionally substituted with 1 to 3 substituents independently        selected from the group consisting of halogen, cyano, nitro,        C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl,        C₂-C₄ haloalkenyl, C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl,        C₂-C₄ alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄        haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄        alkylamino, C₂-C₆ dialkylamino, SF₅, Si(CH₃)₃, CHO, hydroxy,        OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹.    -   Embodiment 7. A compound of Embodiment 6 wherein R¹ is phenyl or        pyridinyl, each optionally substituted with 1 to 3 substituents        independently selected from the group consisting of halogen,        cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄        haloalkyl, C₂-C₄ haloalkenyl, C₂-C₄ alkylcarbonyl, C₂-C₄        haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄        alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,        C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹²,        S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆ dialkylamino, SF₅, Si(CH₃)₃,        CHO, hydroxy, OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹.    -   Embodiment 8. A compound of Embodiment 7 wherein R¹ is phenyl or        pyridinyl, each optionally substituted with 1 to 3 substituents        independently selected from the group consisting of halogen,        cyano, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄        haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹² and S(O)₂R¹³.    -   Embodiment 9. A compound of Formula 1 or any of Embodiments 1-4        wherein R¹ is

-   -   Embodiment 10. A compound of Formula 1 or any of Embodiments 1-4        wherein R¹ is C(X¹)R¹⁸ or C(═NOR²³)R¹⁸.    -   Embodiment 11. A compound of Embodiment 10 wherein R¹ is        C(X¹)R¹⁸.    -   Embodiment 12. A compound of Formula 1 or any of Embodiments        1-11 wherein X¹ is O.    -   Embodiment 13. A compound of Formula 1 or any of Embodiments        1-11 wherein X¹ is S.    -   Embodiment 14. A compound of Embodiment 10 wherein R¹ is        C(═NOR²³)R¹⁸.    -   Embodiment 15. A compound of Formula 1 or any of Embodiments 1-4        wherein R¹ is an 8- to 10-membered heteroaromatic bicyclic ring        system optionally substituted on carbon ring members with up to        3 substituents independently selected from the group consisting        of halogen, cyano, nitro, SF₅, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄        alkynyl, C₁-C₄ haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄        haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄        alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,        C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹²,        S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆ dialkylamino, Si(CH₃)₃, CHO,        hydroxy, OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹, and optionally substituted        on nitrogen ring members with methyl.    -   Embodiment 16. A compound of Formula 1 or any of Embodiments 1-4        wherein R¹ is phenyl or a 5- or 6-membered heteroaromatic ring,        each substituted with GQ¹ and further optionally substituted        with 1 or 2 substituents independently selected from the group        consisting of halogen, cyano, nitro, SF₅, C₁-C₄ alkyl, C₂-C₄        alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄ alkylcarbonyl,        C₂-C₄ haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄        alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,        C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹²,        S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆ dialkylamino, Si(CH₃)₃, CHO,        hydroxy, OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹.    -   Embodiment 17. A compound of Embodiment 16 wherein R¹ is phenyl        or pyridinyl, each substituted with GQ¹ and further optionally        substituted with 1 or 2 substituents independently selected from        the group consisting of halogen, cyano, SF₅, C₁-C₄ alkyl, C₁-C₄        haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄        alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,        C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹²        and S(O)₂R¹³.    -   Embodiment 18. A compound of Formula 1 or any of Embodiments        1-17 wherein Q¹ is phenyl or pyridinyl, each optionally        substituted with 1 to 3 substituents independently selected from        the group consisting of halogen, cyano, C₁-C₄ alkyl, C₁-C₄        haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄        alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,        C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹²        and S(O)₂R¹³.    -   Embodiment 19. A compound of Formula 1 or any of Embodiments 1-4        wherein R¹ is selected from Embodiments 5, 6, 9, 10, 15 and 16.    -   Embodiment 20. A compound of Formula 1 or any of Embodiments        1-19 wherein R² is C₂-C₆ alkyl, C₁-C₆ haloalkyl, CH₂CO₂R²¹,        CR⁵R⁶CH₂OR²¹, CR⁵R⁶CH₂CH₂OR²¹, CR⁵R⁶CH₂S(O)_(n)R²¹ or        CR⁵R⁶CH₂CH₂S(O)_(n)R²¹.    -   Embodiment 21. A compound of Formula 1 or any of Embodiments        1-19 wherein R² is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl,        each optionally substituted with 1 to 4 substituents selected        from the group consisting of halogen, C₁-C₂ alkyl, 1 cyclopropyl        and 1CF₃.    -   Embodiment 22. A compound of Formula 1 or any of Embodiments        1-19 wherein R² is CR⁵R⁶Q.    -   Embodiment 22a. A compound of Formula 1 or any of Embodiments        1-19 wherein R² is selected from Embodiments 20, 21 and 22.    -   Embodiment 23. A compound of Embodiment 20 wherein R² is C₂-C₆        alkyl, C₁-C₆ haloalkyl or CR⁵R⁶CH₂OR²¹.    -   Embodiment 24. A compound of Embodiment 21 wherein R² is C₄-C₇        cycloalkylalkyl optionally substituted with 1 to 4 substituents        selected from the group consisting of halogen, C₁-C₂ alkyl, 1        cyclopropyl and 1CF₃.    -   Embodiment 24a. A compound of Formula 1 or any of Embodiments        1-19 wherein R² is selected from Embodiments 23 and 24.    -   Embodiment 25. A compound of Formula 1 or any of Embodiments        1-24 wherein G is a direct bond.    -   Embodiment 26. A compound of Formula 1 or any of Embodiments        1-25 wherein R³ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆        alkenyl, C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl or        C≡CR¹⁰.    -   Embodiment 27. A compound of Formula 1 or any of Embodiments        1-25 wherein R³ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl,        each optionally substituted with 1 to 4 substituents        independently selected from the group consisting of halogen,        C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃.    -   Embodiment 28. A compound of Embodiment 26 wherein R³ is C₁-C₆        alkyl or C₁-C₆ haloalkyl.    -   Embodiment 29. A compound of Embodiment 28 wherein R³ is CH₃.    -   Embodiment 29a. A compound of Formula 1 or any of Embodiments        1-29 wherein R⁴ is C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl,        C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl or C≡CR¹⁰.    -   Embodiment 29b. A compound of Formula 1 or any of Embodiments        1-29 wherein R⁴ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl,        each optionally substituted with 1 to 4 substituents        independently selected from the group consisting of halogen,        C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃.    -   Embodiment 29c. A compound of Embodiment 29a wherein R⁴ is C₁-C₆        alkyl or C₁-C₆ haloalkyl.    -   Embodiment 29d. A compound of Embodiment 29c wherein R⁴ is CH₃.    -   Embodiment 30. A compound of Formula 1 or any of Embodiments        1-25 wherein R³ and R⁴ are taken together with the contiguous        linking nitrogen and carbon atoms to form an optionally        substituted ring R-1

-   -   -   or ring R-2

-   -   Embodiment 31. A compound of Embodiment 30 wherein R³ and R⁴ are        taken together with the contiguous linking nitrogen and carbon        atoms to form an optionally substituted ring R-1.    -   Embodiment 32. A compound of Embodiment 30 wherein R³ and R⁴ are        taken together with the contiguous linking nitrogen and carbon        atoms to form an optionally substituted ring R-2.    -   Embodiment 32a. A compound of Formula 1 or any of Embodiments        1-25 wherein R³ is selected from Embodiments 26 and 27, and R⁴        is selected from Embodiments 29a and 29b; or R³ and R⁴ are taken        together with the contiguous linking nitrogen and carbon atoms        to form an optionally substituted ring as described in        Embodiment 30.    -   Embodiment 32b. A compound of Formula 1 or any of Embodiments        1-32a wherein m is 2 or 3.    -   Embodiment 32c. A compound of Formula 1 or any of Embodiments        1-32b wherein p is O.    -   Embodiment 32d. A compound of Formula 1 or any of Embodiments        1-32c wherein Z is C(R^(8a))═C(R^(8b)) or S, provided that the        C(R^(8a))═C(R^(8b)) moiety is oriented so the carbon atom bonded        to R^(8b) is connected as R³ in Formula 1.    -   Embodiment 33. A compound of Embodiment 32d wherein Z is CH═CH        or CH═CF, provided that the CH═CF moiety is oriented so the        carbon atom bonded to F is connected as R³ in Formula 1.    -   Embodiment 34. A compound of Embodiment 32d wherein Z is S.    -   Embodiment 35. A compound of Formula 1 or any of Embodiments        1-34 wherein each R⁵ is independently H or C₁-C₄ alkyl.    -   Embodiment 36. A compound of Embodiment 35 wherein each R⁵ is        independently H or methyl.    -   Embodiment 37. A compound of Formula 1 or any of Embodiments        1-36 wherein R⁶ is H.    -   Embodiment 38. A compound of Formula 1 or any of Embodiments        1-37 wherein Q is Q-1, Q-5, Q-6 or Q-9.    -   Embodiment 39. A compound of Embodiment 38 wherein Q is Q-1, Q-5        or Q-9.    -   Embodiment 40. A compound of Embodiment 38 wherein Q is Q-1.    -   Embodiment 41. A compound of Embodiment 38 wherein Q is Q-5.    -   Embodiment 42. A compound of Embodiment 38 wherein Q is Q-6.    -   Embodiment 43. A compound of Embodiment 38 wherein Q is Q-9.    -   Embodiment 44. A compound of any of Embodiments 38, 39, 41 or 43        wherein Z¹ is O.    -   Embodiment 45. A compound of any of Embodiments 38, 39, 41 or 43        wherein Z¹ is S.    -   Embodiment 46. A compound of any of Embodiments 38, 39, 41 or 43        wherein Z¹ is NR¹⁴.    -   Embodiment 47. A compound of Formula 1 or any of Embodiments        1-46 wherein each R^(9a) is independently H, halogen, cyano,        C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy,        SF₅ or S(O)_(n)R¹²; or C₃-C₆ cycloalkyl or C₄-C₇        cycloalkylalkyl, each optionally substituted with 1 to 4        substituents selected from the group consisting of halogen,        C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃.    -   Embodiment 48. A compound of Embodiment 47 wherein each R^(9a)        is independently H, halogen, cyano, C₁-C₄ alkyl, C₁-C₄        haloalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, SF₅ or S(O)_(n)R¹².    -   Embodiment 49. A compound of Embodiment 47 wherein each R^(9a)        is independently C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each        optionally substituted with 1 to 4 substituents selected from        the group consisting of halogen, C₁-C₂ alkyl, 1 cyclopropyl and        1CF₃.    -   Embodiment 50. A compound of Formula 1 or any of Embodiments        1-49 wherein each R^(9b) is independently H, halogen, cyano,        C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₄ alkoxy or C₁-C₄ haloalkoxy.    -   Embodiment 51. A compound of Formula 1r

-   -   wherein        -   X is O or S;        -   Y is O or S;        -   R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆            alkenyl, C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl            or C≡CR¹⁰; or        -   R¹ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents            independently selected from the group consisting of halogen,            C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; or        -   R¹ is phenyl, naphthalenyl or a 5- or 6-membered            heteroaromatic ring, each optionally substituted with 1 to 3            substituents independently selected from the group            consisting of halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆            dialkylamino; or        -   R¹ is

-   -   -   each A is independently C(R¹⁶)₂, O, S or NR¹⁵;        -   each A¹ is independently C(R¹⁷)₂;        -   R² is C₂-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆            haloalkenyl, C₃-C₆ alkynyl, C₃-C₆ haloalkynyl or C₂-C₆            alkoxyalkyl; or        -   R² is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents selected            from the group consisting of halogen, C₁-C₂ alkyl, 1            cyclopropyl and 1CF₃; or        -   R² is CR⁵R⁶Q;        -   R³ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆            haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl or C≡CR¹⁰; or        -   R³ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents            independently selected from the group consisting of halogen,            C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; or        -   R³ is phenyl, naphthalenyl or a 5- or 6-membered            heteroaromatic ring, each optionally substituted with 1 or 2            substituents independently selected from the group            consisting of halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆            dialkylamino;        -   R⁴ is C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆            haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl or C≡CR¹⁰; or        -   R⁴ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents            independently selected from the group consisting of halogen,            C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; or        -   R⁴ is phenyl, naphthalenyl or a 5- or 6-membered            heteroaromatic ring, each optionally substituted with 1 or 2            substituents independently selected from the group            consisting of halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆            dialkylamino; or        -   R³ and R⁴ are taken together with the contiguous linking            nitrogen and carbon atoms to form an optionally substituted            ring R-1

-   -   -   or ring R-2

-   -   -   Z is C(R⁸)═C(R⁸) or S;        -   R⁵ is H, F, Cl, cyano or C₁-C₄ alkyl;        -   R⁶ is H, F, C₁ or CH₃;        -   Q is

-   -   -   Z¹ is O, S or NR¹⁴;        -   R⁷ is H, halogen, cyano, CF₃, C₁-C₃ alkyl or C₃-C₆            cycloalkyl;        -   each R⁸ is independently H or F;        -   each R⁹ is independently H, halogen, cyano, nitro, C₁-C₄            alkyl, C₁-C₄ haloalkyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl,            C₂-C₄ alkynyl, C₂-C₄ haloalkynyl, C₁-C₄ alkoxy, C₁-C₄            haloalkoxy, C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl,            C₂-C₄ alkoxycarbonyl, C₂-C₄ haloalkoxycarbonyl, C(O)NH₂,            C₂-C₄ alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C₂-C₄            haloalkylaminocarbonyl, C₃-C₇ halodialkylaminocarbonyl or            S(O)_(n)R¹²; or        -   each R⁹ is independently C₃-C₆ cycloalkyl or C₄-C₇            cycloalkylalkyl, each optionally substituted with 1 to 4            substituents selected from the group consisting of halogen,            C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; or        -   each R⁹ is independently phenyl or a 5- or 6-membered            heteroaromatic ring, each optionally substituted with 1 or 2            substituents independently selected from the group            consisting of halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆            dialkylamino;        -   each R¹⁰ is independently Si(R¹¹)₃; or phenyl optionally            substituted with halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C₂-C₆ alkoxyalkyl, C₁-C₄ alkoxy, C₁-C₄            haloalkoxy, S(O)_(n)R¹², C₁-C₄ alkylamino or C₂-C₆            dialkylamino;        -   each R¹¹ is independently C₁-C₄ alkyl;        -   each R¹² is independently C₁-C₄ alkyl or C₁-C₄ haloalkyl;        -   R¹⁴ is C₁-C₄ alkyl;        -   each R¹⁵ is independently C₁-C₄ alkyl;        -   each R¹⁶ is independently H or C₁-C₄ alkyl;        -   each R¹⁷ is independently H or F;        -   m is 1, 2 or 3;        -   each n is independently 0, 1 or 2;        -   p is 0, 1, 2, 3 or 4;        -   each r is independently 0, 1 or 2; and        -   v is 1 or 2;        -   provided that (a) when R² is CH₂CH═CH₂, R³ and R⁴ are taken            together to form ring R-2, Z is CH═CH, X is O and Y is O,            then R¹ is other than H, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH═CH₂            or unsubstituted phenyl; (b) when R¹ is H, R³ and R⁴ are            taken together to form ring R-2, Z is CH═CH, X is O and Y is            O, then R² is other than CH₂CH═CH₂ or CH₂C≡CH; (c) when R¹            is CH₂CH₃, R³ and R⁴ are taken together to form ring R-2, Z            is CH═CH, X is O and Y is O, then R² is other than            CH₂(CH₂)₃CH₃; (d) when R³ is H, R² and R⁴ are both            cyclohexyl, X is O and Y is O, then R¹ is other than            CH₃; (e) when R¹ is H or C₁-C₃ n-alkyl, R³ and R⁴ are taken            together to form ring R-2, Z is S, X is O and Y is O, then            R² is other than C₁-C₆ alkyl or C₃-C₄ alkoxyalkyl; (f) when            R² is cyclopropylmethyl, R³ and R⁴ are taken together to            form ring R-2, Z is S, X is O and Y is O, then R¹ is other            than CH₃, CH₂CH₃ or CH₂CH₂CH₃; (g) when R¹ is unsubstituted            phenyl, R³ and R⁴ are taken together to form ring R-2, Z is            S, X is O and Y is O, then R² is other than C₃-C₄            alkoxyalkyl; and (h) when R¹ is Br, R³ and R⁴ are taken            together to form ring R-2, Z is S, X is O and Y is O, then            R² is other than CH₂CH₃.

    -   Embodiment 52. A compound of Embodiment 51 wherein X is O.

    -   Embodiment 53. A compound of Embodiment 51 wherein Y is O.

    -   Embodiment 54. A compound of Embodiment 51 wherein R¹ is phenyl,        naphthalenyl or a 5- or 6-membered heteroaromatic ring, each        optionally substituted with 1 to 3 substituents independently        selected from the group consisting of halogen, cyano, nitro,        C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl,        C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆        alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆        dialkylamino.

    -   Embodiment 55. A compound of Embodiment 54 wherein R¹ is phenyl        optionally substituted with 1 or 2 substituents independently        selected from the group consisting of halogen, cyano, C₁-C₂        haloalkyl, C₁-C₂ alkoxy and C₁-C₂ haloalkoxy.

    -   Embodiment 56. A compound of Embodiment 54 wherein R¹ is 2-, 3-        or 4-pyridinyl optionally substituted with halogen, cyano, C₁-C₂        haloalkyl, C₁-C₂ alkoxy or C₁-C₂ haloalkoxy.

    -   Embodiment 57. A compound of Formula 1r wherein R¹ is

-   -   Embodiment 58. A compound of Embodiment 51 wherein R² is C₂-C₆        alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl or C₃-C₆ haloalkenyl.    -   Embodiment 59. A compound of Embodiment 51 wherein R² is CH₂CF₃        or CR⁵R⁶Q.    -   Embodiment 60. A compound of Embodiment 59 wherein R² is CR⁵R⁶Q.    -   Embodiment 61. A compound of Embodiment 59 wherein R² is CH₂CF₃.    -   Embodiment 62. A compound of Embodiment 51 or Embodiment 60        wherein R⁵ is H or CH₃.    -   Embodiment 63. A compound of Embodiment 51 or Embodiment 60        wherein R⁶ is H.    -   Embodiment 64. A compound of Embodiment 51 wherein Q is Q-1a,        Q-2a, Q-3a, Q-4-a or Q-5a.    -   Embodiment 65. A compound of Embodiment 64 wherein Q is Q-1a or        Q-5a.    -   Embodiment 66. A compound of Embodiment 51 wherein R⁹ is F or        Cl.    -   Embodiment 67. A compound of Embodiment 51 wherein R³ and R⁴ are        taken together with the contiguous linking nitrogen and carbon        atoms to form ring R-2

-   -   Embodiment 68. A compound of Embodiment 51 or Embodiment 67        wherein Z is CH═CH.    -   Embodiment 69. A compound of Embodiment 51 or Embodiment 67        wherein Z is S.    -   Embodiment 70. A compound of Formula 1s

-   -   wherein        -   X is O or S;        -   Y is O or S;        -   R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆            alkenyl, C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl            or C≡CR¹⁰; or        -   R¹ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents            independently selected from the group consisting of halogen,            C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; or        -   R¹ is phenyl, naphthalenyl or a 5- or 6-membered            heteroaromatic ring, each optionally substituted with 1 to 3            substituents independently selected from the group            consisting of halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆            dialkylamino; or        -   R¹ is

-   -   -   each A is independently C(R¹⁶)₂, O, S or NR¹⁵;        -   each A¹ is independently C(R¹⁷)₂;        -   R² is C₂-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆            haloalkenyl, C₃-C₆ alkynyl, C₃-C₆ haloalkynyl or C₂-C₆            alkoxyalkyl; or        -   R² is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents selected            from the group consisting of halogen, C₁-C₂ alkyl, 1            cyclopropyl and 1CF₃; or        -   R² is CR⁵R⁶Q;        -   R³ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆            haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl or C≡CR¹⁰; or        -   R³ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents            independently selected from the group consisting of halogen,            C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; or        -   R³ is phenyl, naphthalenyl or a 5- or 6-membered            heteroaromatic ring, each optionally substituted with 1 or 2            substituents independently selected from the group            consisting of halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆            dialkylamino;        -   R⁴ is C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆            haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl or C≡CR¹⁰; or        -   R⁴ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents            independently selected from the group consisting of halogen,            C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; or        -   R⁴ is phenyl, naphthalenyl or a 5- or 6-membered            heteroaromatic ring, each optionally substituted with 1 or 2            substituents independently selected from the group            consisting of halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆            dialkylamino; or        -   R³ and R⁴ are taken together with the contiguous linking            nitrogen and carbon atoms to form an optionally substituted            ring R-1

-   -   -   or an optionally substituted aromatic ring R-2

-   -   -   Z is C(R⁸)═C(R⁸);        -   R⁵ is H, F, Cl, cyano or C₁-C₄ alkyl;        -   R⁶ is H, F, C₁ and CH₃;        -   Q is

-   -   -   Z¹ is O, S or NR¹⁴;        -   R⁷ is H, halogen, cyano, CF₃, C₁-C₃ alkyl or C₃-C₆            cycloalkyl;        -   each R⁸ is independently H or F;        -   each R⁹ is independently H, halogen, cyano, nitro, C₁-C₄            alkyl, C₁-C₄ haloalkyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl,            C₂-C₄ alkynyl, C₂-C₄ haloalkynyl, C₁-C₄ alkoxy, C₁-C₄            haloalkoxy, C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl,            C₂-C₄ alkoxycarbonyl, C₂-C₄ haloalkoxycarbonyl, C(O)NH₂,            C₂-C₄ alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C₂-C₄            haloalkylaminocarbonyl, C₃-C₇ halodialkylaminocarbonyl or            S(O)_(n)R¹²; or        -   each R⁹ is independently C₃-C₆ cycloalkyl or C₄-C₇            cycloalkylalkyl, each optionally substituted with 1 to 4            substituents selected from the group consisting of halogen,            C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃;        -   each R¹⁰ is independently Si(R¹¹)₃; or phenyl optionally            substituted with halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C₂-C₆ alkoxyalkyl, C₁-C₄ alkoxy, C₁-C₄            haloalkoxy, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆            dialkylamino;        -   each R¹¹ is independently C₁-C₄ alkyl;        -   each R¹² is independently C₁-C₄ alkyl or C₁-C₄ haloalkyl;        -   R¹⁴ is C₁-C₄ alkyl;        -   each R¹⁵ is independently C₁-C₄ alkyl;        -   each R¹⁶ is independently H or C₁-C₄ alkyl;        -   each R¹⁷ is independently H or F;        -   m is 1, 2 or 3;        -   each n is independently 0, 1 or 2;        -   p is 0, 1, 2, 3 or 4;        -   each r is independently 0, 1 or 2; and        -   v is 1 or 2;        -   provided that (a) when R² is CH₂CH═CH₂, R³ and R⁴ are taken            together to form carbocyclic ring R-2, Z is CH═CH, X is O            and Y is O, then R¹ is other than H, CH(CH₃)₂, CH₂CH₂CH₂CH₃,            CH₂CH═CH₂ or unsubstituted phenyl; (b) when R¹ is H, R³ and            R⁴ are taken together to form carbocyclic ring R-2, Z is            CH═CH, X is O and Y is O, then R² is other than CH₂CH═CH₂ or            CH₂C≡CH; (c) when R¹ is CH₂CH₃, R³ and R⁴ are taken together            to form carbocyclic ring R-2, Z is CH═CH, X is O and Y is O,            then R² is other than CH₂(CH₂)₃CH₃; and (d) when R³ is H, R²            and R⁴ are both cyclohexyl, X is O and Y is O, then R¹ is            other than CH₃.

    -   Embodiment 71. A compound of Embodiment 70 wherein X is O.

    -   Embodiment 72. A compound of Embodiment 70 wherein Y is O.

    -   Embodiment 73. A compound of Embodiment 70 wherein R¹ is phenyl,        naphthalenyl or a 5- or 6-membered heteroaromatic ring, each        optionally substituted with 1 to 3 substituents independently        selected from the group consisting of halogen, cyano, nitro,        C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl,        C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆        alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆        dialkylamino.

    -   Embodiment 74. A compound of Embodiment 73 wherein R¹ is phenyl        optionally substituted with 1 or 2 substituents independently        selected from the group consisting of halogen, cyano, C₁-C₂        haloalkyl, C₁-C₂ alkoxy and C₁-C₂ haloalkoxy.

    -   Embodiment 75. A compound of Embodiment 73 wherein R¹ is 2-, 3-        or 4-pyridinyl optionally substituted with halogen, cyano, C₁-C₂        haloalkyl, C₁-C₂ alkoxy and C₁-C₂ haloalkoxy.

    -   Embodiment 76. A compound of Embodiment 70 wherein R¹ is

-   -   Embodiment 77. A compound of Formula 1s wherein R² is C₂-C₆        alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl or C₃-C₆ haloalkenyl.    -   Embodiment 78. A compound of Embodiment 70 wherein R² is CH₂CF₃        or CR⁵R⁶Q.    -   Embodiment 79. A compound of Embodiment 78 wherein R² is CR⁵R⁶Q.    -   Embodiment 80. A compound of Embodiment 78 wherein R² is CH₂CF₃.    -   Embodiment 81. A compound of Embodiment 70 or Embodiment 79        wherein R⁵ is H or CH₃.    -   Embodiment 82. A compound of Embodiment 70 or Embodiment 79        wherein R⁶ is H.    -   Embodiment 83. A compound of Embodiment 70 wherein Q is Q-1a,        Q-2a, Q-3a, Q-4-a or Q-5a.    -   Embodiment 84. A compound of Embodiment 83 wherein Q is Q-1a or        Q-5a.    -   Embodiment 85. A compound of Embodiment 70 wherein R⁹ is F or        Cl.    -   Embodiment 86. A compound of Embodiment 70 wherein R³ and R⁴ are        taken together with the contiguous linking nitrogen and carbon        atoms to form an optionally substituted aromatic ring R-2

-   -   Embodiment 87. A compound of Embodiment 70 or Embodiment 86        wherein Z is CH═CH.

Of note are compounds of Formulae 1, 1r and 1s or any one of Embodiments1-87 wherein X and Y are O, a composition comprising said compound, andits use for controlling an invertebrate pest.

Embodiments of this invention, including Embodiments 1-87 above as wellas any other embodiments described herein, can be combined in anymanner, and the descriptions of variables in the embodiments pertain notonly to the compounds of Formulae 1, 1r and 1s but also to the startingcompounds and intermediate compounds useful for preparing the compoundsof Formulae 1, 1r and 1s. In addition, embodiments of this invention,including Embodiments 1-87 above as well as any other embodimentsdescribed herein, and any combination thereof, pertain to thecompositions and methods of the present invention.

Combinations of Embodiments 1-50 are illustrated by:

-   -   Embodiment A. A compound of Formula 1 wherein        -   X is O;        -   Y is O;        -   R¹ is H or halogen; or        -   R¹ is phenyl or a 6-membered heteroaromatic ring, each            optionally substituted with 1 to 3 substituents            independently selected from the group consisting of halogen,            cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl,            C₁-C₄ haloalkyl, C₂-C₄ haloalkenyl, C₂-C₄ alkylcarbonyl,            C₂-C₄ haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄            alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl,            C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆            dialkylamino, SF₅, Si(CH₃)₃, CHO, hydroxy, OC(O)R¹⁹ and            N(R²⁰)C(O)R¹⁹; or        -   R¹ is

-   -   -    or        -   R¹ is C(X¹)R¹⁸ or C(═NOR²³)R¹⁸; or        -   R¹ is an 8- to 10-membered heteroaromatic bicyclic ring            system optionally substituted on carbon ring members with up            to 3 substituents independently selected from the group            consisting of halogen, cyano, nitro, SF₅, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄            haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄            alkylamino, C₂-C₆ dialkylamino, Si(CH₃)₃, CHO, hydroxy,            OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹, and optionally substituted on            nitrogen ring members with methyl; or        -   R¹ is phenyl or a 5- or 6-membered heteroaromatic ring, each            substituted with GQ¹, each optionally substituted with 1Q²            and each optionally substituted with 1 or 2 substituents            independently selected from the group consisting of halogen,            cyano, nitro, SF₅, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄            alkynyl, C₁-C₄ haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄            haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄            alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl,            C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆            dialkylamino, Si(CH₃)₃, CHO, hydroxy, OC(O)R¹⁹ and            N(R²⁰)C(O)R¹⁹;        -   G is a direct bond;        -   Q¹ is phenyl or a 5- or 6-membered heteroaromatic ring, each            optionally substituted with 1 to 3 substituents            independently selected from the group consisting of halogen,            cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl,            C₁-C₄ haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄            haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄            alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl,            C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆            dialkylamino, SF₅, Si(CH₃)₃, CHO, hydroxy, OC(O)R¹⁹ and            N(R²⁰)C(O)R¹⁹;        -   R² is C₂-C₆ alkyl, C₁-C₆ haloalkyl, CH₂CO₂R²¹, CR⁵R⁶CH₂OR²¹,            CR⁵R⁶CH₂CH₂OR²¹, CR⁵R⁶CH₂S(O)_(n)R²¹ or            CR⁵R⁶CH₂CH₂S(O)_(n)R²¹; or        -   R² is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents selected            from the group consisting of halogen, C₁-C₂ alkyl, 1            cyclopropyl and 1CF₃; or        -   R² is CR⁵R⁶Q;        -   R³ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆            haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl or C≡CR¹⁰; or        -   R³ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents            independently selected from the group consisting of halogen,            C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃;        -   R⁴ is C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆            haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl or C≡CR¹⁰; or        -   R⁴ is C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl, each            optionally substituted with 1 to 4 substituents            independently selected from the group consisting of halogen,            C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; or        -   R³ and R⁴ are taken together with the contiguous linking            nitrogen and carbon atoms to form an optionally substituted            ring R-1

-   -   -   or ring R-2

-   -   -   Z is C(R^(8a))═C(R^(8b)) or S, provided that the            C(R^(8a))═C(R^(8b)) moiety is oriented so the carbon atom            bonded to R^(8b) is connected as R³ in Formula 1;        -   each R⁵ is independently H, F, Cl, cyano or C₁-C₄ alkyl;        -   each R⁶ is independently H, F, C₁ or CH₃; and        -   Q is

-   -   Embodiment B. A compound of Embodiment A wherein        -   X is O; and        -   Y is O.    -   Embodiment C. A compound of Embodiment B wherein        -   R³ is C₁-C₆ alkyl or C₁-C₆ haloalkyl; and        -   R⁴ is C₁-C₆ alkyl or C₁-C₆ haloalkyl.    -   Embodiment D. A compound of Embodiment C wherein        -   R³ is CH₃; and        -   R⁴ is CH₃.    -   Embodiment E. A compound of Embodiment B wherein        -   R³ and R⁴ are taken together with the contiguous linking            nitrogen and carbon atoms to form an optionally substituted            ring R-1;        -   m is 2 or 3; and        -   p is 0.    -   Embodiment F. A compound of Embodiment B wherein        -   R³ and R⁴ are taken together with the contiguous linking            nitrogen and carbon atoms to form an optionally substituted            ring R-2; and        -   Z is CH═CH or CH═CF, provided that the CH═CF moiety is            oriented so the carbon atom bonded to F is connected as R³            in Formula 1.    -   Embodiment G. A compound of Embodiment B wherein        -   R³ and R⁴ are taken together with the contiguous linking            nitrogen and carbon atoms to form an optionally substituted            ring R-2; and        -   Z is S.    -   Embodiment H. A compound of any one of Embodiments C-G wherein        -   R¹ is H or halogen.    -   Embodiment I. A compound of any one of Embodiments C-G wherein        -   R¹ is phenyl or pyridinyl, each optionally substituted with            1 to 3 substituents independently selected from the group            consisting of halogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄            alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄ haloalkenyl,            C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄            alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇            dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄            haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄            alkylamino, C₂-C₆ dialkylamino, SF₅, Si(CH₃)₃, CHO, hydroxy,            OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹.    -   Embodiment J. A compound of Embodiment I wherein        -   R¹ is phenyl or pyridinyl, each optionally substituted with            1 to 3 substituents independently selected from the group            consisting of halogen, cyano, C₁-C₄ alkyl, C₁-C₄ haloalkyl,            C₂-C₄ alkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄            alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl,            C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹² and S(O)₂R¹³.    -   Embodiment K. A compound of any one of Embodiments C-G wherein        -   R¹ is C(X¹)R¹⁸ or C(═NOR²³)R¹⁸; and        -   X¹ is O.    -   Embodiment L. A compound of any one of Embodiments C-G wherein        -   R¹ is phenyl or pyridinyl, each substituted with GQ¹ and            further optionally substituted with 1 or 2 substituents            independently selected from the group consisting of halogen,            cyano, nitro, SF₅, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄            alkynyl, C₁-C₄ haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄            haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄            alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl,            C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆            dialkylamino, Si(CH₃)₃, CHO, hydroxy, OC(O)R¹⁹ and            N(R²⁰)C(O)R¹⁹.    -   Embodiment M. A compound of Embodiment L wherein        -   R¹ is phenyl or pyridinyl, each substituted with GQ¹ and            further optionally substituted with 1 or 2 substituents            independently selected from the group consisting of halogen,            cyano, SF₅, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₂-C₄            alkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄            alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl,            C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹² and S(O)₂R¹³; and        -   Q¹ is phenyl or pyridinyl, each optionally substituted with            1 to 3 substituents independently selected from the group            consisting of halogen, cyano, C₁-C₄ alkyl, C₁-C₄ haloalkyl,            C₂-C₄ alkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄            alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl,            C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆            alkoxyalkyl, S(O)_(n)R¹² and S(O)₂R¹³.    -   Embodiment N. A compound of any one of Embodiments C-G wherein        -   R² is C₂-C₆ alkyl, C₁-C₆ haloalkyl or CR⁵R⁶CH₂OR²¹; or        -   R² is C₄-C₇ cycloalkylalkyl optionally substituted with 1 to            4 substituents selected from the group consisting of            halogen, C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃.    -   Embodiment O. A compound of any one of Embodiments C-G wherein        -   R² is CR⁵R⁶Q.    -   Embodiment P. A compound of Embodiment O wherein        -   Q is Q-1, Q-5, Q-6 or Q-9;        -   R⁵ is H or methyl;        -   R⁶ is H;        -   each R^(9a) is independently H, halogen, cyano, C₁-C₄ alkyl,            C₁-C₄ haloalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, SF₅ or            S(O)_(n)R¹²; or C₃-C₆ cycloalkyl or C₄-C₇ cycloalkylalkyl,            each optionally substituted with 1 to 4 substituents            selected from the group consisting of halogen, C₁-C₂ alkyl,            1 cyclopropyl and 1CF₃; and        -   each R^(9b) is independently H, halogen, cyano, C₁-C₄ alkyl,            C₁-C₄ haloalkyl, C₁-C₄ alkoxy or C₁-C₄ haloalkoxy.        -   Combinations of Embodiments 51-69 are illustrated by:    -   Embodiment A1. A compound of Formula 1r

-   -   wherein    -   X is O;    -   Y is O; and    -   R³ and R⁴ are taken together with the contiguous linking        nitrogen and carbon atoms to form ring R-2

-   -   Embodiment B1. A compound of Embodiment A1 wherein    -   R¹ is phenyl, naphthalenyl or a 5- or 6-membered heteroaromatic        ring, each optionally substituted with 1 to 3 substituents        independently selected from the group consisting of halogen,        cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄        haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆        alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆        dialkylamino; or    -   R¹ is

-   -   Embodiment C1. A compound of Embodiment B1 wherein    -   R² is C₂-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl or C₃-C₆        haloalkenyl; or    -   R² is CR⁵R⁶Q; and    -   Q is Q-1a, Q-2a, Q-3a, Q-4-a or Q-5a.    -   Embodiment D1. A compound of Embodiment C1 wherein    -   Z is CH═CH;    -   R¹ is phenyl optionally substituted with 1 or 2 substituents        independently selected from the group consisting of halogen,        cyano, C₁-C₂ haloalkyl, C₁-C₂ alkoxy and C₁-C₂ haloalkoxy;    -   R² is CH₂CF₃ or CR⁵R⁶Q;    -   R⁵ is H or CH₃;    -   Q is Q-1a or Q-5a;    -   R⁶ is H;    -   R⁹ is F or Cl; and    -   r is 1.    -   Embodiment E1. A compound of Embodiment C1 wherein    -   Z is S;    -   R¹ is phenyl optionally substituted with 1 or 2 substituents        independently selected from the group consisting of halogen,        cyano, C₁-C₂ haloalkyl, C₁-C₂ alkoxy and C₁-C₂ haloalkoxy;    -   R² is CH₂CF₃ or CR⁵R⁶Q;    -   R⁵ is H or CH₃;    -   Q is Q-1a or Q-5a;    -   R⁶ is H;    -   R⁹ is F or Cl; and    -   r is 1.

Combinations of Embodiments 70-87 are illustrated by:

-   -   Embodiment A2. A compound of Formula 1s

-   -   wherein    -   X is O;    -   Y is O; and    -   R³ and R⁴ are taken together with the contiguous linking        nitrogen and carbon atoms to form an optionally substituted        aromatic ring R-2

-   -   Embodiment B2. A compound of Embodiment A2 wherein    -   R¹ is phenyl, naphthalenyl or a 5- or 6-membered heteroaromatic        ring, each optionally substituted with 1 to 3 substituents        independently selected from the group consisting of halogen,        cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄        haloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄        alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇        dialkylaminocarbonyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆        alkoxyalkyl, S(O)_(n)R¹², C₁-C₄ alkylamino and C₂-C₆        dialkylamino; or    -   R¹ is

-   -   Embodiment C2. A compound of Embodiment B2 wherein    -   R² is C₂-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl or C₃-C₆        haloalkenyl; or    -   R² is CR⁵R⁶Q; and    -   Q is Q-1a, Q-2a, Q-3a, Q-4-a or Q-5a.    -   Embodiment D2. A compound of Embodiment C2 wherein    -   Z is CH═CH;    -   R¹ is phenyl optionally substituted with 1 or 2 substituents        independently selected from the group consisting of halogen,        cyano, C₁-C₂ haloalkyl, C₁-C₂ alkoxy and C₁-C₂ haloalkoxy;    -   R² is CH₂CF₃ or CR⁵R⁶Q;    -   R⁵ is H or CH₃;    -   Q is Q-1a or Q-5a;    -   R⁶ is H;    -   R⁹ is F or Cl; and    -   r is 1.

Specific embodiments include compounds of Formula 1 selected from thegroup consisting of:

-   3-(2,4-difluorophenyl)-2-hydroxy-4-oxo-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(4-fluorophenyl)-2-hydroxy-4-oxo-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-chloro-3-pyridinyl)methyl]-3-(2,4-difluorophenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-chloro-3-pyridinyl)methyl]-3-(4-fluorophenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(3-chlorophenyl)-1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-3-[3-(trifluoromethyl)phenyl]-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-3-[3-(trifluoromethoxy)phenyl]-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-(4-fluorophenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-(2,4-difluorophenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-3-(4-methoxyphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-3-(3-methoxyphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-fluoro-3-pyridinyl)methyl]-3-(4-fluorophenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(3-bromophenyl)-1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(3-bromophenyl)-1-[(6-chloro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-chloro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-3-[3-(trifluoromethoxy)phenyl]-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-3-[4-(trifluoromethyl)-2-pyridinyl]-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-(2-cyanophenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   8-[(6-chloro-3-pyridinyl)methyl]-7-hydroxy-5-oxo-6-phenyl-5H-thiazolo[3,2-a]pyrimidinium    inner salt;-   8-[(6-chloro-3-pyridinyl)methyl]-6-(4-fluorophenyl)-7-hydroxy-5-oxo-5H-thiazolo[3,2-a]pyrimidinium    inner salt;-   8-[(6-chloro-3-pyridinyl)methyl]-7-hydroxy-5-oxo-6-[3-(trifluoromethoxy)phenyl]-5H-thiazolo[3,2-a]pyrimidinium    inner salt;-   8-[(2-chloro-5-thiazolyl)methyl]-7-hydroxy-5-oxo-6-phenyl-5H-thiazolo[3,2-a]pyrimidinium    inner salt;-   8-[(2-chloro-5-thiazolyl)methyl]-6-(4-fluorophenyl)-7-hydroxy-5-oxo-5H-thiazolo[3,2-a]pyrimidinium    inner salt;-   8-[(2-chloro-5-thiazolyl)methyl]-7-hydroxy-5-oxo-6-[3-(trifluoromethoxy)phenyl]-5H-thiazolo[3,2-a]pyrimidinium    inner salt;-   3-[3-(6-chloro-3-pyridinyl)phenyl]-1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-fluoro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-3-[3-(trifluoromethoxy)phenyl]-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(5-chloro-2-fluorophenyl)-1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-[2-chloro-5-(trifluoromethoxy)phenyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(4-fluorophenyl)-2-hydroxy-1-[(1-methyl-1H-pyrazol-4-yl)methyl]-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   2-hydroxy-1-[(1-methyl-1H-pyrazol-4-yl)methyl]-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dimethoxyphenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-[2-fluoro-5-(trifluoromethoxy)phenyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(2-chloro-4-pyridinyl)-1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-(2-fluoro-5-bromophenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-3-(2,4,5-trifluorophenyl)-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-[3-bromo-5-(trifluoromethoxy)phenyl]-1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-[3-bromo-5-(trifluoromethyl)phenyl]-1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-3-(2-methoxyphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-(2-fluorophenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-chloro-3-pyridinyl)methyl]-3-(2-fluorophenyl)-2-hydroxy-4-oxo-5H-thiazolo[3,2-a]pyrimidinium    inner salt;-   2-hydroxy-4-oxo-3-phenyl-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-[(6-chloro-3-pyridinyl)methyl]-5-(4-fluorophenyl)-3,6-dihydro-4-hydroxy-1,2-dimethyl-6-oxopyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-[3-(6-fluoro-3-pyridinyl)-5-(trifluoromethyl)phenyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[1-(6-chloro-3-pyridinyl)ethyl]-3-(4-fluorophenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(2-chloro-5-thiazolyl)methyl]-3-(ethoxycarbonyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-benzoyl-1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(2,4-difluorophenyl)-1-[(6-fluoro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-chloro-3-pyridinyl)methyl]-2-hydroxy-3-(3-methoxyphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-chloro-3-pyridinyl)methyl]-3-(2,3-difluorophenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-chloro-3-pyridinyl)methyl]-3-(2-fluoro-3-methoxyphenyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(3,5-dimethoxyphenyl)-1-[(6-fluoro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-fluoro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-3-[3-(trifluoromethyl)phenyl]-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(4-fluorophenyl)-2-hydroxy-1-[(2-methyl-5-thiazolyl)methyl]-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   2-hydroxy-4-oxo-3-phenyl-1-[(5-thiazolyl)methyl]-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(4-fluorophenyl)-2-hydroxy-4-oxo-1-[(5-thiazolyl)methyl]-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(2-fluorophenyl)-1-[(6-fluoro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-chloro-3-pyridinyl)methyl]-3-[2-chloro-5-(trifluoromethyl)phenyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   3-(2-fluoro-4-cyanophenyl)-1-[(6-fluoro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt;-   1-[(6-fluoro-3-pyridinyl)methyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidinium    inner salt; and-   1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-3-[3-(6-trifluoromethyl-3-pyridinyl)phenyl]-4H-pyrido[1,2-a]pyrimidinium    inner salt.

Of note is that compounds of this invention are characterized byfavorable metabolic and/or soil residual patterns and exhibit activitycontrolling a spectrum of agronomic and nonagronomic invertebrate pests.

Of particular note, for reasons of invertebrate pest control spectrumand economic importance, protection of agronomic crops from damage orinjury caused by invertebrate pests by controlling invertebrate pestsare embodiments of the invention. Compounds of this invention because oftheir favorable translocation properties or systemicity in plants alsoprotect foliar or other plant parts which are not directly contactedwith a compound of Formula 1 or a composition comprising the compound.

Also noteworthy as embodiments of the present invention are compositionscomprising a compound of any of the preceding Embodiments, as well asany other embodiments described herein, and any combinations thereof,and at least one additional component selected from the group consistingof a surfactant, a solid diluent and a liquid diluent, said compositionsoptionally further comprising at least one additional biologicallyactive compound or agent.

Further noteworthy as embodiments of the present invention arecompositions for controlling an invertebrate pest comprising abiologically effective amount of a compound of any of the precedingEmbodiments, as well as any other embodiments described herein, and anycombinations thereof, and at least one additional component selectedfrom the group consisting of a surfactant, a solid diluent and a liquiddiluent, said compositions optionally further comprising a biologicallyeffective amount of at least one additional biologically active compoundor agent.

Embodiments of the invention also include a composition for protectingan animal comprising a compound (i.e. in a parasiticidally effectiveamount) of any of the preceding Embodiments and a carrier.

Embodiments of the invention further include methods for controlling aninvertebrate pest comprising contacting the invertebrate pest or itsenvironment with a biologically effective amount of a compound of any ofthe preceding Embodiments (e.g., as a composition described herein). Ofparticular note is a method for protecting an animal comprisingadministering to the animal a parasiticidally effective amount of acompound of any of the preceding Embodiments (e.g., as a compositiondescribed herein).

Embodiments of the invention also include a composition comprising acompound of any of the preceding Embodiments, in the form of a soildrench liquid formulation. Embodiments of the invention further includemethods for controlling an invertebrate pest comprising contacting thesoil with a liquid composition as a soil drench comprising abiologically effective amount of a compound of any of the precedingEmbodiments.

Embodiments of the invention also include a spray composition forcontrolling an invertebrate pest comprising a biologically effectiveamount of a compound of any of the preceding Embodiments and apropellant. Embodiments of the invention further include a baitcomposition for controlling an invertebrate pest comprising abiologically effective amount of a compound of any of the precedingEmbodiments, one or more food materials, optionally an attractant, andoptionally a humectant. Embodiments of the invention also include adevice for controlling an invertebrate pest comprising said baitcomposition and a housing adapted to receive said bait composition,wherein the housing has at least one opening sized to permit theinvertebrate pest to pass through the opening so the invertebrate pestcan gain access to said bait composition from a location outside thehousing, and wherein the housing is further adapted to be placed in ornear a locus of potential or known activity for the invertebrate pest.

Embodiments of the invention also include a method for protecting a seedfrom an invertebrate pest comprising contacting the seed with abiologically effective amount of a compound of any of the precedingEmbodiments (e.g., as a composition described herein).

Embodiments of the invention also include methods for protecting ananimal from an invertebrate parasitic pest comprising administering tothe animal a parasiticidally effective amount of a compound of any ofthe preceding Embodiments.

Embodiments of the invention also include methods for controlling aninvertebrate pest comprising contacting the invertebrate pest or itsenvironment with a biologically effective amount of a compound ofFormula 1, an N-oxide or a salt thereof, (e.g., as a compositiondescribed herein), provided that the methods are not methods of medicaltreatment of a human or animal body by therapy.

This invention also relates to such methods wherein the invertebratepest or its environment is contacted with a composition comprising abiologically effective amount of a compound of Formula 1, an N-oxide ora salt thereof, and at least one additional component selected from thegroup consisting of surfactants, solid diluents and liquid diluents,said composition optionally further comprising a biologically effectiveamount of at least one additional biologically active compound or agent,provided that the methods are not methods of medical treatment of ahuman or animal body by therapy.

One or more of the following methods and variations as described inSchemes 1-19 can be used to prepare the compounds of Formula 1. Thedefinitions of R¹, R², R³, R⁴, R⁹, R¹⁰, R¹⁸, R²³, X and Y in thecompounds of Formulae 1-22 below are as defined above in the Summary ofthe Invention unless otherwise noted. Formulae 1a-1l are various subsetsof Formula 1, and all substituents for Formulae 1a-1l are as definedabove for Formula 1 unless otherwise indicated. Ambient or roomtemperature is defined as about 20-25° C.

Compounds of Formula 1a (i.e. Formula 1 wherein X and Y are O) can beprepared by condensation of appropriately substituted compounds ofFormula 2 with optionally substituted malonic acids (3a) in the presenceof condensing agents as shown in Scheme 1. Condensing agents can becarbodiimides such as dicyclohexyl carbodiimide (see, for example, Koch,A. et al. Tetrahedron 2004, 60, 10011-10018) or other agents well knownin the art to form amide bonds with or without activating agents such asN-hydroxybenzotriazole as described in Science of Synthesis 2005, 21,17-25 and Tetrahedron 2005, 61, 10827-10852. This reaction is typicallycarried out in an inert organic solvent, such as dichloromethane or1,2-dichloroethane, at temperatures from about 0 to about 80° C. for aperiod of 10 min to several days.

Compounds of Formula 1a can also be prepared by the condensation ofcompounds of Formula 2 with malonic acid esters (3b) wherein R is aC₁-C₅ alkyl group, preferably a C₁-C₄ alkyl group, as shown in Scheme 2.These reactions can be performed neat or in the presence of inertsolvents as described in Bulletin of the Chemical Society of Japan 1999,72(3), 503-509. Inert solvents include, but are not limited to, highboiling hydrocarbons such as mesitylene, tetralin or cymene, or highboiling ethers such as diphenyl ether. Typical temperatures range from50 to 250° C. Of note are temperatures from 150 to 200° C., whichtypically provide rapid reaction times and high yields. These reactionscan also be performed in microwave reactors within the same temperatureranges. Typical reaction times range from 5 min to several hours.

Compounds of the Formula 3a can be prepared by a variety of methodsknown in the art, for example by base hydrolysis of compounds of Formula3b. Compounds of Formula 3b can be prepared by arylation of malonateesters catalyzed by palladium (J. Org. Chem 2002, 67, 541-555) or copper(Org. Lett. 2002, 4, 269-272 and Org. Lett. 2005, 7, 4693-4695).

Compounds of Formula 1a can also be prepared by treatment of compoundsof Formula 2 with activated esters of Formula 3c wherein LvO is anactivated leaving group as shown in Scheme 3. Examples of Lv preferredfor ease of synthesis or reactivity are 2,4,6-trichlorophenyl,pentachlorophenyl or pentafluorophenyl as described in Archiv derPharmazie (Weinheim, Germany) 1991, 324, 863-6. Other activated estersare well known in the art and include, but are not limited to,N-hydroxysuccinimide esters (see, for example, J. Am. Chem. Soc. 2002,124, 6872-6878). Typical temperatures range from 50 to 200° C. Of noteare temperatures from 50 to 150° C., which typically provide rapidreaction times and high yields. These reactions can be performed with orwithout solvent, such as toluene, and in microwave reactors within thesame temperature ranges. Typical reaction times range from 5 min to 2 h.

Compounds of the Formula 3c can be prepared, for example, from compoundsof Formula 3a (see, for example, J. Het. Chem. 1980, 17, 337).

Compounds of Formula 1a can also be prepared by condensation ofcompounds of Formula 2 with compounds of Formulas 3d or 3e, or bycondensation of compounds of Formula 2 with mixtures of compounds ofFormulae 3d and 3e as shown in Scheme 4. These reactions are typicallyperformed in an inert solvent, such as dichloromethane, and optionallyin the presence of two or more equivalents of an acid acceptor (see, forexample, Zeitschrift für Naturforschung, Teil B: Anorganische Chemie,Organische Chemie 1982, 37B(2), 222-33). Typical acid acceptors include,but are not limited to, triethylamine, N,N-diisopropylethylamine,pyridine and substituted pyridines.

Compounds of Formula 1b (i.e. Formula 1a wherein R¹ is H) can beprepared by condensation of compounds of Formula 2 with carbon suboxide(3f) (see, for example, J. Org. Chem. 1972, 37(9), 1422-5) as shown inScheme 5. The reactions are typically performed in an inert solvent suchas ether and can include the use of a catalyst such as AlCl₃.

Compounds of Formula 2 can be prepared in a variety of ways known in theart; see, for example, Patai, S. The Chemistry of Functional Groups: TheChemistry of Amidines and Imidates; Wiley: Chichester, UK, 1975; TheChemistry of Amidines and Imidates; Patai, S.; Rappoport, Z., Eds.;Wiley: Chichester, UK, 1991; Vol. 2; Mega, T. et al. Bulletin of theChemical Society of Japan 1988, 61(12), 4315-21; Ife, R. et al. EuropeanJournal of Medicinal Chemistry 1989, 24(3), 249-57; Wagaw, S.; Buchwald,S. Journal of Organic Chemistry 1996, 61(21), 7240-7241; Shen, Q. et al.Angewandte Chemie, International Edition 2005, 44(9), 1371-1375; andOkano, K. et al. Organic Letters 2003, 5(26), 4987-4990.

Compounds of Formula 1a wherein R¹ is CR²⁴═C(R²⁴)R¹⁰, optionallysubstituted phenyl, naphthalenyl, a 5- or 6-membered heteroaromatic ringor an 8- to 10-membered heteroaromatic bicyclic ring system can beprepared from compounds of Formula 1d (i.e. Formula 1 wherein R¹ is Cl,Br or I, preferably wherein R¹ is Br or I) and compounds of Formula 4wherein M with R¹ forms a boronic acid, boronic acid ester ortrifluoroborate salt, or M is trialkylstannyl or zinc and R¹ isCR²⁴═C(R²⁴)R¹⁰, optionally substituted phenyl, naphthalenyl, a 5- or6-membered heteroaromatic ring or an 8- to 10-membered heteroaromaticbicyclic ring system as shown in Scheme 6.

Compounds of Formula 1e (i.e. Formula 1a wherein R² is CR⁵R⁶Q, and Q isa heterocycle substituted with a phenyl or a 5- or 6-memberedheteroaromatic ring) can be prepared from compounds of Formula 1f andcompounds of Formula 4a wherein M with R^(9c) forms a boronic acid,boronic acid ester or trifluoroborate salt, or M is trialkylstannyl orzinc and R^(9c) is a phenyl or a 5- or 6-membered heteroaromatic ring asshown in Scheme 7.

Compounds of Formula 1g (i.e. Formula 1a wherein R¹ is phenyl or pyridylsubstituted with GQ¹ and G is a direct bond) can be prepared fromcompounds of Formula 1h (i.e. Formula 1a wherein R¹ is phenylsubstituted with Br or I) and compounds of Formula 4b wherein M with Q¹forms a boronic acid, boronic acid ester or trifluoroborate salt, or Mis trialkylstannyl or zinc, and Q¹ is a phenyl or 5- or 6-memberedheteroaromatic ring) as shown in Scheme 8.

The reactions of Schemes 6, 7 and 8 are typically carried out in thepresence of a palladium catalyst and a base optionally under an inertatmosphere. The palladium catalysts used for the reactions of Schemes 6,7 and 8 typically comprises palladium in a formal oxidation state ofeither 0 (i.e. Pd(0)) or 2 (i.e. Pd(II)). A wide variety of suchpalladium-containing compounds and complexes are useful as catalysts forthese reactions. Examples of palladium-containing compounds andcomplexes useful as catalysts in the methods of Schemes 7, 8 and 9include PdCl₂(PPh₃)₂ (bis(triphenylphosphine)palladium (II) dichloride),Pd(PPh₃)₄ (tetrakis(triphenylphosphine)palladium(0)), Pd(C₅H₇O₂)₂(palladium(II) acetyl-acetonate), Pd₂(dba)₃(tris(dibenzylideneacetone)dipalladium(0)), and[1,1′-bis(diphenyl-phosphino)ferrocene]dichloropalladium(II). Themethods of Schemes 6, 7 and 8 are generally conducted in a liquid phase,and therefore to be most effective the palladium catalyst preferably hasgood solubility in the liquid phase. Useful solvents include, forexample, water, ethers such as 1,2-dimethoxyethane, amides such asN,N-dimethyl-acetamide, and non-halogenated aromatic hydrocarbons suchas toluene.

The methods of Schemes 6, 7 and 8 can be conducted over a wide range oftemperatures, ranging from about 25 to about 200° C. Of note aretemperatures from about 60 to about 150° C., which typically providefast reaction times and high product yields. The general methods andprocedures for Stille, Negishi and Suzuki couplings with aryl iodides,bromides or chlorides and an aryl tin, aryl zinc or aryl boronic acidrespectively are well known in the literature; see, for example, E.Negishi, Handbook of Organopalladium Chemistry for Organic Synthesis,Wiley-Interscience, 2002, New York, N.Y.

Compounds of Formula 1a wherein R¹ is optionally substituted phenyl,naphthalenyl, a 5- or 6-membered heteroaromatic ring or an 8- to10-membered heteroaromatic bicyclic ring system can be prepared fromcompounds of Formula 1b (i.e. Formula 1a wherein R¹ is H) and compoundsof Formula 5 wherein X¹ is Cl, Br or I (preferably wherein X¹ is Br orI) as shown in Scheme 9.

These reactions are typically carried out in the presence of a coppercatalyst optionally under an inert atmosphere. The copper catalysts usedfor the present method typically comprise copper in metallic form (e.g.,as a powder) or copper in a formal oxidation state of 1 (i.e. Cu(I)).Examples of copper-containing compounds useful as catalysts in themethod of Scheme 9 include, but are not limited to, Cu, CuI, CuBr, CuCl.Useful solvents for the method of Scheme 9 include, for example, etherssuch as 1,4-dioxane, amides such as N,N-dimethylacetamide and dimethylsulfoxide.

The method of Scheme 9 can be conducted over a wide range oftemperatures from 25 to 200° C. Of note are temperatures from 40 to 150°C. The method of Scheme 9 can be conducted in the presence of a ligand.A wide variety of such copper-binding compounds are useful as ligandsfor the present method. Examples of useful ligands include, but are notlimited to, 1,10-phenanthroline, N,N-dimethylethylenediamine, L-prolineand 2-picolinic acid. The general methods and procedures forcopper-catalyzed Ullmann-type coupling reactions are well known in theliterature; see, for example, Xie, Ma, et al. Org. Lett. 2005, 7,4693-4695.

Compounds of Formula 1i can be prepared from compounds of Formula 1b bycarbonylation with compounds of Formula 6 as shown in Scheme 10.Examples of carbonylation agents of Formula 6 useful in the method ofScheme 10 include, but are not limited to, aliphatic or aromaticcarboxylic acids, acid anhydrides, acid halides, isocyanates andisothiocyanates. Typically the reaction is performed in an inertsolvent, more typically a polar solvent such as N,N-dimethylacetamide or1-methyl-2-pyrrolidinone. The reaction is typically performed attemperatures from 0 to 180° C., more typically at ambient temperature to150° C. Microwave irradiation can be advantageous in heating thereaction mixture.

Compounds of the Formula 1j can be prepared by reacting compounds ofFormula 1i with an alkoxyamine salt of the Formula 7, where X³ is acounterion such as halide or oxalate, as shown in Scheme 11. Thereaction can be run in an alcoholic solvent such as ethanol or propanolat temperatures ranging from 80° C. to the reflux temperature of thesolvent in 3 to 24 hours.

Compounds of Formula 1a wherein R¹ is C(═NNR²⁰R²³)R¹⁸,C(═NNR²⁰C(O)R²³)R¹⁸, C(═NNR²⁰C(O)OR^(23a))R¹⁸ or C(═NNR²⁰C(O)NR²⁰R²³)R¹⁸can be prepared from compounds of Formula 1i and the appropriatelysubstituted hydrazine by the method shown in Scheme 11.

Compounds of Formula 1a wherein R¹ is C₂-C₆ alkynyl, C₂-C₆ haloalkynylor C≡CR¹⁰ can be prepared from compounds of Formula 1d (i.e. Formula 1awherein R¹ is Cl, Br or I) and substituted alkynes of Formula 8 by aSonigashira coupling reaction as shown in Scheme 12. Sonigashiracouplings are well known in the literature. See, for example, K.Sonogashira, Sonogashira Alkyne Synthesis Vol 2, p. 493 in E. Negishi,Handbook of Organopalladium Chemistry for Organic Synthesis,Wiley-Interscience, 2002, New York, N.Y.

Compounds of Formula 1d can be prepared from compounds of Formula 1b byhalogenation using, for example, liquid bromine or N-halosuccinimides(9) as shown in Scheme 13. Typically the reaction is performed in aninert solvent, more typically a halogenated solvent such as methylenechloride or 1,2-dichloroethane. The reaction is typically performed attemperatures from 0 to 80° C., more typically at ambient temperature.

Compounds of Formula 1k (i.e. Formula 1a wherein R³ and R⁴ are takentogether to form an optionally substituted carbocyclic ring R-1 whereinm is 2) can be prepared from compounds of Formula 1l (i.e. Formula 1wherein R³ and R⁴ are taken together to form an optionally substitutedaromatic ring R-2 wherein Z is CH═CH) by reduction using hydrogen in thepresence of a platinum group metal or metal oxide catalyst as shown inScheme 14. Typically the platinum group metal is platinum or palladiumor their oxides and the reduction is performed in an inert solvent (see,for example, Kappe, Thomas, et al. Heterocycles 1995, 40, 681-9).Suitable solvents include, but are not limited to, methanol, ethanol,tetrahydrofuran and methyl t-butyl ether. The reaction is typicallyperformed at ambient temperature and at approximately 100 kPa ofpressure.

Compounds of Formula 1l can be prepared from compounds of Formula 2(wherein R³ and R⁴ are taken together with the contiguous linkingnitrogen and carbon atoms to form ring R-1 and Z is CH═CH) by themethods shown in Schemes 1 through 5.

Compounds of Formula 1a can also be prepared by alkylation of compoundsof Formula 10 using appropriately substituted alkylating agents andbases such as potassium carbonate as shown in Scheme 15 (see, forexample, Kappe, T. et al. Monatschefte fur Chemie 1971, 102, 412-424 andUrban, M. G.; Arnold, W. Helvetica Chimica Acta 1970, 53, 905-922).Alkylating agents include, but are not limited to, alkyl chlorides,bromides, iodides and sulfonate esters. A wide variety of bases andsolvents can be employed in the method of Scheme 15, and these bases andsolvents are well known in the art.

Compounds of Formula 10 can be prepared from compounds of Formula 2a bymethods analogous to those shown in Schemes 1 through 5. Compounds ofFormula 2a are commercially available or can be prepared by generalmethods well known in the art.

One skilled in the art will appreciate that compounds of Formula 2wherein R³ and R⁴ are taken together to form ring R-2 and wherein R^(a)is the subset of R² substituents containing a terminal CH₂ group can beprepared by general methods well known in the art. For example, Scheme16 illustrates a method wherein a compound of Formula 12 is acylatedwith a compound of Formula 13 in the presence of an appropriate base.The resulting intermediate of Formula 14 is reduced with an appropriatereagent such as diborane to provide the compound of Formula 11.

Compounds of Formula 11a (compounds of Formula 11 where Z is CH═CH) canbe prepared by direct displacement reaction of alpha-halopyridinecompounds of Formula 15 by suitable amines of Formula 16 as shown inScheme 17. Examples of alpha-halopyridine compounds useful in the methodof Scheme 17 include, but are not limited to, 2-fluoropyridine and2-chloropyridine. Examples of suitable amines include, but are notlimited to, 2,2,2-trifluoroethylamine and5-aminomethyl-2-chloropyridine. Typically the reaction is performed inan inert solvent, more typically a polar solvent such asN,N-dimethylacetamide or 1-methyl-2-pyrrolidinone. The reaction istypically performed at temperatures from 0 to 250° C., more typically atambient temperature to 150° C. Alternatively, the reaction can beperformed in a sealed tube in a laboratory microwave reactor; typicalreaction temperatures are from 200 to 240° C. The hydrochloride salts ofthe compounds of Formula 15 are suitable starting materials for thismethod.

Compounds of Formula 11 can be prepared by reductive amination reactionbetween amines of Formula 12 and suitable aldehydes of Formula 17. Thesereactions are either performed in one-pot or by stepwise reaction viathe imine intermediate of Formula 18 as shown in Scheme 18. Examples ofamine compounds useful in the method of Scheme 18 include, but are notlimited to, 2-aminopyridine and 2-aminothiazole. Examples of suitablealdehydes in the method of Scheme 18 include, but are not limited to,6-chloronicotinaldehyde. Examples of suitable reducing agents in themethod of Scheme 18 include, but are limited to, sodium borohydride,zinc borohydride and sodium cyanoborohydride. General methods andprocedures for reductive amination reactions are well known in theliterature; see, for example, Abdel-Magid, et al. J. Org. Chem. 1996,61(11), 3849-3862.

An alternative method for the preparation of compounds of Formula 11 isshown in Scheme 19. In the method of Scheme 19, compounds of Formula 12are protected with suitable protecting groups such as, but not limitedto, tert-butoxycarbonyl, acetyl or formyl to form the intermediate ofFormula 20 wherein PG is a protecting group. The compound of Formula 20is then alkylated with an appropriate reagent of Formula 21 (whereinR^(a) is the subset of R² substituents containing a terminal CH₂ groupand X⁵ is a leaving group such as a halogen) to give an intermediate ofFormula 22. The protecting group is removed to provide a compound ofFormula 11. Conditions for the formation and removal of protectinggroups on an amine function are known in the literature (see, forexample, Greene, T. W.; Wuts, P. G. M. Protective Groups in OrganicSynthesis, 2nd ed.; Wiley: New York, 1991).

Compounds of Formula 1 wherein X and/or Y are S can be prepared fromcorresponding compounds of Formula 1a by general methods known in theart involving treatment with thionating reagents such as P₄S₁₀ orLawessen's Reagent(2,4-bis-(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide).Alternatively, malonic acids of Formula 3a can be treated withP₂S₆(CH₃)₂ as described in J. Am. Chem. Soc. 1988, 110 (4), 1316-1318.The resulting malonic acid sulfur derivatives can then be used toprepare the compounds of Formula 1 wherein X and/or Y are S by themethod of Scheme 1.

Schemes 1 through 19 illustrate methods to prepare compounds of Formula1 having a variety of substituents noted for R¹, R², R³ and R⁴.Compounds of Formula 1 having R¹, R², R³ and R⁴ substituents other thanthose particularly noted for Schemes 1 through 19 can be prepared bygeneral methods known in the art of synthetic organic chemistry,including methods analogous to those described for Schemes 1 to 19.

Examples of intermediates useful in the preparation of compounds of thisinvention are shown in Tables I-1 through I-19. The followingabbreviations are used in the Tables which follow: Me means methyl, Etmeans ethyl and C(O)O(2,4,6-trichlorophenyl) means

TABLE I-1

R^(x) is C(O)OH and R^(y) is H R^(a) R^(b) R^(c) R^(d) R^(e) H H H H H FH H H H H F H H H H H F H H OMe H H H H H OMe H H H H H OMe H H F F H HH F H F H H F H H F H F H H H F Cl H H H H H Cl H H H H H Cl H H H Br HH H H I H H H H Cl H Cl H H Cl H Br H H Cl H OCF₃ H H Cl H CF₃ H H Br HBr H H Br H OCF₃ H H Br H CF₃ H H H cyano H H F H cyano H H H OCF₃ H H HH CF₃ H H H H SCF₃ H H H F H H Cl H F H H Br H F H H OCF₃ H F H H CF₃ HF H H OMe H F H H SCF₃ H Cl H H OCF₃ H Cl H H CF₃ H H H H SF₅ H Cl H HSF₅ H H OCF₂H H H H H H OCF₂H H H F F H F H F H F H F F H F F H F F F HH H OMe H OMe H F OMe H H H OMe H H Cl H OMe H H Br H OMe H H OCF₃ H OMeH H CF₃ H H CF₃ H CF₃ H Me H H H H H Me H H H H H Me H H H6-fluoro-3-pyridinyl H H H H 6-chloro-3-pyridinyl H H H H6-bromo-3-pyridinyl H H H H 6-trifluoromethyl-3-pyridinyl H H H H

H H H H 6-fluoro-3-pyridinyl H OMe H H 6-chloro-3-pyridinyl H OMe H H6-bromo-3-pyridinyl H OMe H H 6-trifluoromethyl-3-pyridinyl H OMe H H6-fluoro-3-pyridinyl H CF₃ H H 6-chloro-3-pyridinyl H CF₃ H H6-bromo-3-pyridinyl H CF₃ H H 6-trifluoromethyl-3-pyridinyl H CF₃ H H6-fluoro-3-pyridinyl H Br H H 6-chloro-3-pyridinyl H Br H H6-bromo-3-pyridinyl H Br H H 6-trifluoromethyl-3-pyridinyl H Br H H6-fluoro-3-pyridinyl H Cl H H 6-chloro-3-pyridinyl H Cl H H6-bromo-3-pyridinyl H Cl H H 6-trifluoromethyl-3-pyridinyl H Cl H H6-fluoro-3-pyridinyl OMe H H H 6-chloro-3-pyridinyl OMe H H H6-bromo-3-pyridinyl OMe H H H 6-trifluoromethyl-3-pyridinyl OMe H H H6-fluoro-3-pyridinyl F H H H 6-chloro-3-pyridinyl F H H H6-bromo-3-pyridinyl F H H H 6-trifluoromethyl-3-pyridinyl F H H SCF₃ H HCl H SCF₃ H H Br H SCF₃ H H OCF₃ H SCF₃ H H CF₃ H SCF₃ H H SCF₃ H SCF₃ HH 6-trifluoromethyl-3-pyridinyl H SCF₃ H H 6-fluoro-3-pyridinyl H SCF₃ HH 6-chloro-3-pyridinyl H SCF₃ H H 6-bromo-3-pyridinyl H

Table I-2

Table I-2 is constructed the same as Table I-1, except that R^(x) isC(O)OMe and R^(y) is H.

Table I-3

Table I-3 is constructed the same as Table I-1, except that R^(x) isC(O)OEt and R^(y) is H.

Table I-4

Table I-4 is constructed the same as Table I-1, except that R^(x) isC(O)OH and R^(y) is C(O)OH.

Table I-5

Table I-5 is constructed the same as Table I-1, except that R^(x) isC(O)OH and R^(y) is C(O)OMe.

Table I-6

Table I-6 is constructed the same as Table I-1, except that R^(x) isC(O)OH and R^(y) is C(O)OEt.

Table I-7

Table I-7 is constructed the same as Table I-1, except that R^(x) isC(O)OH and R^(y) is C(O)OC(CH₃)₃.

Table I-8

Table I-8 is constructed the same as Table I-1, except that R^(x) isC(O)C1 and R^(y) is C(O)C1.

Table I-9

Table I-9 is constructed the same as Table I-1, except that R^(x) isC(O)OMe and R^(y) is C(O)OMe.

Table I-10

Table I-10 is constructed the same as Table I-1, except that R^(x) isC(O)OEt and R^(y) is C(O)OEt.

Table I-11

Table I-11 is constructed the same as Table I-1, except that R^(x) isC(O)OC(CH₃)₃ and R^(y) is C(O)OC(CH₃)₃.

Table I-12

Table I-12 is constructed the same as Table I-1, except that R^(x) isC(O)O(2,4,6-trichlorophenyl) and R^(y) is C(O)O(2,4,6-trichlorophenyl).

Table I-12a

Table I-12a is constructed the same as Table I-1, except that R^(x) is Hand R^(y) is C(O)OC(CH₃)₃.

TABLE I-13

R^(x) R^(y) H C(O)OH H C(O)OMe H C(O)OEt C(O)OH C(O)OH C(O)Cl C(O)ClC(O)O(2,4,6-trichlorophenyl) C(O)O(2,4,6-trichlorophenyl) H C(O)OC(CH₃)₃C(O)OMe C(O)OMe C(O)OEt C(O)OEt C(O)OC(CH₃)₃ C(O)OC(CH₃)₃ C(O)OH C(O)OMeC(O)OH C(O)OEt C(O)OH C(O)OC(CH₃)₃

TABLE I-14

R^(x) R^(y) H C(O)OH H C(O)OMe H C(O)OEt C(O)OH C(O)OH C(O)Cl C(O)ClC(O)O(2,4,6-trichlorophenyl) C(O)O(2,4,6-trichlorophenyl) H C(O)OC(CH₃)₃C(O)OMe C(O)OMe C(O)OEt C(O)OEt C(O)OC(CH₃)₃ C(O)OC(CH₃)₃ C(O)OH C(O)OMeC(O)OH C(O)OEt C(O)OH C(O)OC(CH₃)₃

TABLE I-15

R^(x) R^(y) H C(O)OH H C(O)OMe H C(O)OEt C(O)OH C(O)OH C(O)Cl C(O)ClC(O)O(2,4,6-trichlorophenyl) C(O)O(2,4,6-trichlorophenyl) H C(O)OC(CH₃)₃C(O)OMe C(O)OMe C(O)OEt C(O)OEt C(O)OC(CH₃)₃ C(O)OC(CH₃)₃ C(O)OH C(O)OMeC(O)OH C(O)OEt C(O)OH C(O)OC(CH₃)₃

TABLE I-16

R^(x) R^(y) H C(O)OH H C(O)OMe H C(O)OEt C(O)OH C(O)OH C(O)Cl C(O)ClC(O)O(2,4,6-trichlorophenyl) C(O)O(2,4,6-trichlorophenyl) H C(O)OC(CH₃)₃C(O)OMe C(O)OMe C(O)OEt C(O)OEt C(O)OC(CH₃)₃ C(O)OC(CH₃)₃ C(O)OH C(O)OMeC(O)OH C(O)OEt C(O)OH C(O)OC(CH₃)₃

TABLE I-17

R^(x) R^(y) H C(O)OH H C(O)OMe H C(O)OEt C(O)OH C(O)OH C(O)Cl C(O)ClC(O)O(2,4,6-trichlorophenyl) C(O)O(2,4,6-trichlorophenyl) H C(O)OC(CH₃)₃C(O)OMe C(O)OMe C(O)OEt C(O)OEt C(O)OC(CH₃)₃ C(O)OC(CH₃)₃ C(O)OH C(O)OMeC(O)OH C(O)OEt C(O)OH C(O)OC(CH₃)₃

TABLE I-18

R^(x) R^(y) H CF₃ Me CF₃ H Et Me Et H 3-pyridinyl Me 3-pyridinyl H6-fluoro-3-pyridinyl Me 6-fluoro-3-pyridinyl H 6-bromo-3-pyridinyl Me6-bromo-3-pyridinyl H 2-methyl-5-thiazolyl Me 2-methyl-5-thiazolyl H2-chloro-5-thiazolyl Me 2-chloro-5-thiazolyl H 1-methyl-4-pyrazolyl Me1-methyl-4-pyrazolyl H CH₂CHFCF₂Cl Me CH₂CHFCF₂Cl H cyclopropyl Mecyclopropyl H 6-methyl-3-pyridinyl Me 6-methyl-3-pyridinyl H6-chloro-3-pyridinyl Me 6-chloro-3-pyridinyl H 5-thiazolyl Me5-thiazolyl H 2-fluoro-5-thiazolyl Me 2-fluoro-5-thiazolyl H2-bromo-5-thiazolyl Me 2-bromo-5-thiazolyl H 3-methyl-5-isoxazolyl Me3-methyl-5-isoxazolyl

TABLE I-19

R^(x) R^(y) H CF₃ Me CF₃ H Et Me Et H 3-pyridinyl Me 3-pyridinyl H6-fluoro-3-pyridinyl Me 6-fluoro-3-pyridinyl H 6-bromo-3-pyridinyl Me6-bromo-3-pyridinyl H 2-methyl-5-thiazolyl Me 2-methyl-5-thiazolyl H2-chloro-5-thiazolyl Me 2-chloro-5-thiazolyl H 1-methyl-4-pyrazolyl Me1-methyl-4-pyrazolyl H CH₂CHFCF₂Cl Me CH₂CHFCF₂Cl H cyclopropyl Mecyclopropyl H 6-methyl-3-pyridinyl Me 6-methyl-3-pyridinyl H6-chloro-3-pyridinyl Me 6-chloro-3-pyridinyl H 5-thiazolyl Me5-thiazolyl H 2-fluoro-5-thiazolyl Me 2-fluoro-5-thiazolyl H2-bromo-5-thiazolyl Me 2-bromo-5-thiazolyl H 3-methyl-5-isoxazolyl Me3-methyl-5-isoxazolyl

It is recognized that some reagents and reaction conditions describedabove for preparing compounds of Formula 1 may not be compatible withcertain functionalities present in the intermediates. In theseinstances, the incorporation of protection/deprotection sequences orfunctional group interconversions into the synthesis will aid inobtaining the desired products. The use and choice of the protectinggroups will be apparent to one skilled in chemical synthesis (see, forexample, Greene, T. W.; Wuts, P. G. M. Protective Groups in OrganicSynthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art willrecognize that, in some cases, after the introduction of a given reagentas it is depicted in any individual scheme, it may be necessary toperform additional routine synthetic steps not described in detail tocomplete the synthesis of compounds of Formula 1. One skilled in the artwill also recognize that it may be necessary to perform a combination ofthe steps illustrated in the above schemes in an order other than thatimplied by the particular sequence presented to prepare the compounds ofFormula 1.

One skilled in the art will also recognize that compounds of Formula 1and the intermediates described herein can be subjected to variouselectrophilic, nucleophilic, radical, organometallic, oxidation, andreduction reactions to add substituents or modify existing substituents.

Without further elaboration, it is believed that one skilled in the artusing the preceding description can utilize the present invention to itsfullest extent. The following Synthesis Examples are, therefore, to beconstrued as merely illustrative, and not limiting of the disclosure inany way whatsoever. Steps in the following Synthesis Examples illustratea procedure for each step in an overall synthetic transformation, andthe starting material for each step may not have necessarily beenprepared by a particular preparative run whose procedure is described inother Examples or Steps. Ambient or room temperature is defined as about20-25° C. Percentages are by weight except for chromatographic solventmixtures or where otherwise indicated. Parts and percentages forchromatographic solvent mixtures are by volume unless otherwiseindicated. ¹H NMR spectra are reported in ppm downfield fromtetramethylsilane; “s” means singlet, “d” means doublet, “dd” meansdoublet of doublets, “ddd” means doublet of doublet of doublets, “t”means triplet, “m” means multiplet, and “br s” means broad singlet. Formass spectral data, the numerical value reported is the molecular weightof the parent molecular ion (M) formed by addition of H⁺ (molecularweight of 1) to the molecule to give a M+1 peak observed by massspectrometry using atmospheric pressure chemical ionization (AP⁺).

Synthesis Example 1 Preparation of2-hydroxy-4-oxo-3-phenyl-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]-pyrimidiniuminner salt

A mixture of diethyl phenylmalonate (0.62 g, 2.7 mmol) andN-(2,2,2-trifluoroethyl)-2-pyridinamine (0.87 g, 2.7 mmol, prepared bythe method of Bissell, E. R.; Swanslger, R. W. J. Chem. Eng. Data. 1981,26, 234-235) was heated to 180° C. for 2 h. After cooling, the reactionmixture was purified by chromatography on silica gel by elution withethyl acetate to provide the title compound (compound number 7), acompound of this invention, as a yellow solid (45 mg).

¹H NMR (CDCl₃) δ 9.61 (dd, 1H), 8.17 (ddd, 1H), 7.74 (d, 2H), 7.55 (d,1H), 7.45 (t, 1H), 7.39 (m, 2H), 7.21-7.25 (m, 1H), 5.10 (br s, 2H).

Synthesis Example 2 Preparation of1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]-pyrimidiniuminner salt and1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-3-(2,2,2-trifluoroacetyl)-4H-pyrido[1,2-a]pyrimidiniuminner salt Step A: Preparation of 1,1-dimethylethylN-[(2-chloro-5-thiazolyl)methyl]-N-2-pyridinylcarbamate (alternativelynamed 2-chlorothiazol-5-ylmethyl)pyridin-2-yl-carbamic acid t-butylester)

Sodium hydride in mineral oil (60%, 2.22 g, 55.6 mmol) was addedportionwise to a solution of 1,1-dimethylethyl N-2-pyridinylcarbamate(9.0 g, 46.3 mmol, prepared by the method of Krein, D. M.; Lowary, T. L.J. Org. Chem. 2002, 67, 4965-4967) in N,N-dimethylformamide (40 mL) in around bottom flask cooled to 0° C. in an ice/water bath. The suspensionwas stirred vigorously for an additional 30 min, followed by theaddition of 2-chloro-5-(chloromethyl)thiazole (7.4 g, 55.6 mmol). Thereaction mixture was gradually warmed to room temperature and stirredfor 16-24 h. Water (200 mL) was then added, and the reaction mixture wasextracted three times with 50 mL of ethyl acetate. The combined organicextracts were washed four times with 20 mL of water, dried over Na₂SO₄,and concentrated under reduced pressure. The resulting residue waspurified by chromatography on silica gel by elution with ethylacetate/hexane to provide the title compound as an amber oil (9.3 g).

¹H NMR (CDCl₃) δ 8.40 (d, 1H), 7.78 (d, 1H), 7.64 (t, 1H), 7.49 (s, 1H),7.03 (t, 1H), 5.18 (s, 2H), 1.54 (s, 9H).

Step B: Preparation of N-[(chloro-5-thiazolyl)methyl]-2-pyridinamine(alternatively named (2-chlorothiazol-5-ylmethyl)-pyridin-2-yl-amine)

Trifluoroacetic acid (13.2 mL, 171 mmol) was added to a solution of1,1-dimethylethyl

N-[(2-chloro-5-thiazolyl)methyl]-N-2-pyridinylcarbamate (i.e. theproduct of Step A) (9.3 g, 28.5 mmol) in dichloromethane:water (60 mL:8mL) in a round bottom flask, and the mixture was stirred for 66 h. Thereaction mixture was then cooled to 0° C. and neutralized with 3 M NaOHto approximately pH 12 before being extracted twice with 100 mL of ethylacetate. The organic layers were combined, dried over Na₂SO₄, andconcentrated under reduced pressure to provide the title compound as atan solid (5.0 g).

¹H NMR (CDCl₃) δ 8.19 (d, 1H), 7.43 (m, 2H), 7.65 (t, 1H), 6.42 (d, 1H),4.80 (s, NH), 4.67 (d, 2H).

Step C: Preparation of1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt

A solution of dicyclohexylcarbodiimide (1.0 M in dichloromethane, 26.6mL, 26.6 mmol) was added to a solution ofN-[(chloro-5-thiazolyl)methyl]-2-pyridinamine (i.e. the product of StepB) (3.0 g, 13.3 mmol) and malonic acid (1.38 g, 13.3 mmol) indichloromethane (30 mL) in a round bottom flask. The reaction mixturewas stirred at room temperature for 16-24 h. The reaction mixture wasthen filtered through a pad of Celite® diatomaceaus filter aid, and thefiltration cake was washed with dichloromethane. The combined organicphases were concentrated under reduced pressure, and the resultingresidue was purified by chromatography on silica gel by elution withethyl acetate/hexane to provide the title compound (compound number125), a compound of this invention, as a pale yellow solid (2.90 g).

¹H NMR (CD₃S(O)CD₃) δ 9.20 (d, 1H), 8.36 (t, 1H), 8.11 (d, 1H), 7.95 (s,1H), 7.52 (t, 1H), 5.56 (s, 2H), 4.98 (s, 1H).

Step D: Preparation of1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-3-(2,2,2-trifluoroacetyl)-4H-pyrido[1,2-a]pyrimidiniuminner salt

1-[(2-Chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt (i.e. the product of Step C) (300 mg, 1.02 mmol),1,4-diazabicyclo[2.2.2]octane (11.5 mg, 0.102 mmol), and trifluoroaceticanhydride (0.14 mL, 1.02 mmol) were dissolved inN-methyl-2-pyrrolidinone (3 mL), and the reaction mixture was stirred atroom temperature for 1 h. The mixture was diluted with dichloromethane(30 mL), washed with water (10 mL), saturated aqueous sodium bicarbonate(10 mL) and water (10 mL×4 times), concentrated and triturated withdiethyl ether to yield the title compound (compound number 702), acompound of this invention, as a solid (98 mg).

¹H NMR (CD₃COCD₃) δ 9.38 (d, 1H), 8.58 (t, 1H), 8.22 (d, 1H), 7.94 (s,1H), 7.70 (t, 1H), 5.71 (br s, 2H).

Synthesis Example 3 Preparation of1-[(6-chloro-3-pyridinyl)methyl]-3-[2-fluoro-5-(trifluoromethoxy)phenyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt,1-[(6-chloro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt and1-[(6-chloro-3-pyridinyl)methyl]-2-hydroxy-3-iodo-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt Step A: Preparation of6-chloro-N-2-pyridinyl-3-pyridinemethanamine

A mixture of 2-fluoropyridine (1.4 g, 15 mmol) and6-chloro-3-pyridinemethanamine (alternatively named5-aminomethyl-2-chloropyridine) (2.55 g, 18 mmol) inN-methylpyrrolidinone (5 mL) was heated at 230° C. in a microwavereactor for 30 min. This reaction was repeated four times using the sameamounts of starting materials for each repetition. All five of thereaction mixtures were then poured into saturated aqueous sodiumbicarbonate solution and extracted into ethyl acetate. The organic layerwas washed with saturated aqueous sodium bicarbonate solution, driedover Na₂SO₄, and concentrated under reduced pressure. The crude productwas then purified by chromatography on silica gel using 10% ethylacetate in hexanes as the eluent to provide the title compound as an oil(5.1 g).

¹H NMR (CDCl₃) δ 8.38 (s, 1H), 8.1 (m, 1H), 7.67 (d, 1H), 7.42 (dd, 1H),7.28 (d, 1H), 6.63 (m, 1H), 6.38 (d, 1H), 4.88 (s, 1H), 4.56 (d, 2H).

Step B: Preparation of1-[(6-chloro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt

A solution of dicyclohexylcarbodiimide (4.12 g, 20 mmol in 10 mL ofdichloromethane) was added to a solution of6-chloro-N-2-pyridinyl-3-pyridinemethanamine (i.e. the product of StepA) (2.19 g, 10 mmol) and malonic acid (1.04 g, 10 mmol) indichloromethane (10 mL) in a round bottom flask. The reaction mixturewas stirred at room temperature for 16-24 h. The reaction mixture wasthen filtered, and the filtration cake was washed with diethyl ether.The filtrate was concentrated under reduced pressure, and the resultingresidue was washed with methanol to provide the title compound (compoundnumber 611), a compound of this invention, as a pale yellow solid (2.54g).

¹H NMR (acetone-d₆) δ 9.32 (d, 1H), 8.52 (s, 1H), 8.29 (dd, 1H), 7.79(m, 2H), 7.52 (t, 1H), 7.42 (d, 1H), 5.63 (s, 2H), 5.03 (s, 1H).

Step C: Preparation of1-[(6-chloro-3-pyridinyl)methyl]-2-hydroxy-3-iodo-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt

N-iodosuccinimide (1.12 g, 5 mmol) was added to a solution of1-[(6-chloro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt (i.e. the product of Step B) (1.4 g, 5 mmol) inN,N-dimethylformamide (10 mL) and stirred for 5 min. Water was added,and the mixture was extracted with dichloromethane. The combined organicphases were washed repeatedly with water, dried over Na₂SO₄, andconcentrated under reduced pressure. The resulting crude product(compound number 118), a compound of this invention, (1.8 g) was used inthe next step without further purification.

¹H NMR (CDCl₃) δ 9.49 (d, 1H), 8.45 (d, 1H), 8.12 (dd, 1H), 7.40 (m,2H), 7.32 (d, 1H), 5.50 (s, 2H).

Step D: Preparation of1-[(6-chloro-3-pyridinyl)methyl]-3-[2-fluoro-5-(trifluoromethoxy)phenyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt

1-[(6-Chloro-3-pyridinyl)methyl]-2-hydroxy-3-iodo-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt (i.e. the product of Step C) (206 mg, 0.5 mmol),2-fluoro-5-(trifluoromethoxy)benzeneboronic acid (224 mg, 1 mmol) andbis(triphenylphosphino)-palladium dichloride (35 mg, 0.005 mmol) weredissolved in dioxane (2 mL). Aqueous sodium carbonate solution (2 N, 1mL) was added, and the reaction mixture was heated in a microwavereactor for 10 min at 160° C. The cooled reaction mixture was poureddirectly onto a silica gel column and eluted successively with hexanes,30% ethyl acetate in hexanes, 50% ethyl acetate in hexanes, and finallyethyl acetate to yield the title compound (compound number 58), acompound of this invention, as a solid (20 mg).

¹H NMR (CDCl₃) δ 9.53 (d, 1H), 8.49 (s, 1H), 8.11 (dd, 1H), 7.69 (d,1H), 7.50 (d, 1H), 7.41 (m, 2H), 7.34 (d, 1H), 7.16 (d, 2H), 7.58 (br s,2H).

Synthesis Example 4 Preparation of2-hydroxy-4-oxo-3-phenyl-1-(2-propen-1-yl)-4H-pyrido[1,2-a]pyrimidiniuminner salt

N-2-propen-1-yl-2-pyridinamine (670 mg, 5 mmol) and1,3-bis(2,4,6-trichlorophenyl) 2-phenylpropanedioate (3.0 g, 6 mmol)were dissolved in dioxane (3 mL) and heated at 60° C. for 15 min. Thereaction mixture was then poured onto a silica gel column, which waseluted with 50% ethyl acetate in hexanes to provide the title compound(compound number 122), a compound of this invention, as a solid (14 mg).

¹H NMR (CDCl₃) δ 9.52 (d, 1H), 8.04 (dd, 1H), 7.76 (d, 1H), 7.2-7.45 (m,6H), 5.95 (m, 1H), 5.34 (d, 1H), 5.30 (d, 1H), 5.01 (d, 2H).

Synthesis Example 5 Preparation of2-hydroxy-4-oxo-3-phenyl-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]-pyrimidiniuminner salt Step A: Preparation ofN-(2,2,2-trifluoroethyl)-2-pyridinamine

A mixture of 2-fluoropyridine (2.00 g, 20.6 mmol) and2,2,2-trifluoroethylamine hydrogen chloride (5.00 g, 36.9 mmol) washeated to 220° C. for 30 min in a microwave reactor. The same reactionwas repeated 5 times. The reaction mixtures from all 6 reactions werecooled, combined and diluted with ethyl acetate (150 mL). The organicmixture was neutralized by washing with saturated aqueous sodiumbicarbonate, water (30 mL) and brine (30 mL). The organic phase wasdried over Na₂SO₄ and concentrated, and the resulting residue waspurified by chromatography on silica gel using 80% ethyl acetate/hexaneas eluant to give the title compound as a white solid (17.0 g).

¹H NMR (CDCl₃) δ 8.15 (d, 1H), 7.45 (dd, 1H), 6.69 (dd, 1H), 6.49 (d,1H), 4.58 (br s, 1H), 4.11 (q, 2H).

Step B: Preparation of 1,3-bis(2,4,6-trichlorophenyl)2-phenylpropanedioate

To a slurry of phenylmalonic acid (5.00 g, 27.8 mmol) in dichloromethane(7 mL) at room temperature was added a drop of N,N-dimethylformamide,followed by the dropwise addition of oxalyl chloride (9.09 g, 71.6 mmol)at such a rate to keep gas evolution under control. The reaction mixturewas stirred for an additional hour at room temperature, during whichtime the reaction mixture clarified. 2,4,6-Trichlorophenol (15 g, 76mmol) was added, and the reaction mixture was stirred at roomtemperature for 18 h. The reaction mixture was concentrated undervacuum, and methanol (100 mL) was added to the residue, which resultedin precipitation of a large amount of solid. The solid was collected byfiltration, rinsed with methanol (80 mL) and air dried to give the titleproduct as a white solid (13 g).

¹H NMR (CDCl₃) δ 7.64-7.62 (m, 2H), 7.46-7.43 (m, 3H), 7.36 (s, 4H),5.32 (s, 1H).

Step C: Preparation of2-hydroxy-4-oxo-3-phenyl-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]-pyrimidiniuminner salt

A solution of N-(2,2,2-trifluoroethyl)-2-pyridinamine (i.e. the productof Step A) (2.00 g, 11.4 mmol) and 1,3-bis(2,4,6-trichlorophenyl)2-phenylpropanedioate (i.e. the product of Step B) (6.40 g, 11.9 mmol)in toluene (40 mL) was refluxed for 1 h. The reaction mixture was cooledin an ice-water bath with stirring for 2 h. The solid that precipitatedwas collected by filtration, rinsed with diethyl ether and air dried togive the title compound (compound number 7), a compound of thisinvention, as a yellow solid (3.44 g).

¹H NMR (CD₃S(O)CD₃) δ 9.37 (d, 1H), 8.42 (m, 1H), 8.11 (d, 1H), 7.66 (d,2H), 7.61 (m, 1H), 7.32 (t, 2H), 7.18 (t, 1H), 5.35 (q, 2H).

Synthesis Example 6 Preparation of8-[(6-chloro-3-pyridinyl)methyl]-7-hydroxy-5-oxo-6-[3-(trifluoromethoxy)phenyl]-5H-thiazolo[3,2-a]pyrimidiniuminner salt Step A: Preparation ofN-[(6-chloro-3-pyridinyl)methylene]-2-thiazolamine

2-Aminothiazole (0.75 g, 7.5 mmol) was added to2-chloropyridine-6-carboxaldehyde (1.0 g, 7.1 mmol) in dichloromethane(25 mL) at room temperature. The suspension was stirred an additional 10min and then concentrated to dryness under vacuum. The resulting residuewas heated to 90° C. on a rotory evaporator with a non-returning bumptrap to facilitate water removal. After 30 min the resultant yellowsolid was checked by NMR to verify reaction completion (by disappearanceof the characteristic aldehyde peak at 10.10 ppm (s, 1H)). The titlecompound was obtained as a yellow solid (1.55 g) and used in the nextstep without further purification.

¹H NMR (CDCl₃) δ 9.10 (s, 1H), 8.84 (d, 1H), 8.35-8.32 (dd, 1H),7.72-7.70 (d, 1H), 7.48-7.46 (d, 1H), 7.32-7.31 (d, 1H).

Step B: Preparation of 6-chloro-N-2-thiazolyl-3-pyridinemethanamine

N-[(6-chloro-3-pyridinyl)methylene]-2-thiazolamine (i.e. the product ofStep A) (0.55 g, 2.46 mmol) was added portionwise to a stirred excess ofsodium borohydride (0.45 g, 11.8 mmol) in methanol (30 mL). Additionalportions of sodium borohydride (2×1 equivalent) were added during theaddition of the imine to maintain an exothermic reaction. After additionwas complete, the reaction mixture was allowed to stir for 5 min atambient temperature. The excess reducing agent was quenched by addingglacial acetic acid until gas evolution ceased. The clear reactionmixture was concentrated, and the resulting residue was partitionedbetween saturated aqueous sodium carbonate and ethyl acetate. Theaqueous phase was extracted with ethyl acetate (3×30 mL), and thecombined organic phases were washed with brine, dried (MgSO₄) andconcentrated to give the title compound as a tan powder (0.55 g).

¹H NMR (CDCl₃) δ 8.39 (d, 1H), 7.71-7.68 (dd, 1H), 7.30-7.28 (d, 1H),6.98 (d, 1H), 6.48 (d, 1H), 4.48 (s, 2H).

Step C: Preparation of 2-[3-(trifluoromethoxy)phenyl]propanedioic acid

Diethyl 3-trifluoromethoxyphenylmalonate (3.00 g, 9.38 mmol) was stirredin an aqueous sodium hydroxide solution (15 g, 20% by weight) at 65° C.for 10 min. The reaction mixture was then cooled in an ice bath, and ice(7 g) was added to the reaction mixture, followed by 6 N hydrochloricacid to adjust the pH to about 2. The aqueous mixture was saturated withsodium chloride and extracted with ethyl acetate three times. Thecombined organic phases were dried (MgSO₄) and concentrated to give asolid, which was triturated with a mixture of 33% diethyl ether/hexaneto give the title compound as a white solid (2.24 g).

¹H NMR (CD₃C(O)CD₃) δ 11.51 (br s, 2H), 7.54-7.51 (m, 3H), 7.35-7.30 (m,1H), 4.91 (s, 1H).

Step D: Preparation of8-[(6-chloro-3-pyridinyl)methyl]-7-hydroxy-5-oxo-6-[3-(trifluoromethoxy)phenyl]-5H-thiazolo[3,2-a]pyrimidiniuminner salt

Oxalyl chloride (1.0 mL, 11 mmol) was added dropwise at ambienttemperature to a slurry of 2-[3-(trifluoromethoxy)phenyl]propanedioicacid (i.e. the product of Step C) (0.17 g, 0.66 mmol) in dichloromethane(0.2 mL) containing a catalytic amount of N,N-dimethylformamide. Thereaction mixture was stirred for an additional 10 min during which timegas evolution ceased. The reaction mixture was briefly concentratedunder vacuum at ambient temperature. The resultant oil was taken up indichloromethane (2 mL) and added to a solution of6-chloro-N-2-thiazolyl-3-pyridinemethanamine (i.e. the product of StepB) (0.23 g, 1.02 mmol) and triethylamine (0.40 g, 3.37 mmol) indichloromethane (4 mL) at 0° C. After stirring for 15 min, the reactionmixture was concentrated, and the resultant residue was purified bychromatography on silica gel using 50-100% ethyl acetate/hexane aseluant to give the title compound (compound number 138), a compound ofthis invention, as a solid (0.19 g).

¹H NMR (CDCl₃) δ 8.50 (s, 1H), 8.25 (d, 1H), 7.87 (d, 1H), 7.75 (d, 1H),7.70 (s, 1H), 7.41-7.35 (m, 2H), 7.08 (d, 1H), 7.03 (d, 1H), 5.29 (s,2H).

Synthesis Example 7 Preparation of2-hydroxy-4-oxo-1-propyl-3-[2-(trifluoromethyl)phenyl]-4H-pyrido[1,2-a]-pyrimidiniuminner salt and 2-hydroxy-4-oxo-1-propyl-4H-pyrido[1,2-a]-pyrimidiniuminner salt Step A: Preparation of2-hydroxy-4-oxo-1-propyl-4H-pyrido[1,2-a]-pyrimidinium inner salt

A solution of dicyclohexylcarbodiimide (15.63 g in 45 mL ofdichloromethane, 75.76 mmol) was added to a solution ofN-propyl-2-aminopyridine (5.16 g, 37.8 mmol) and malonic acid (3.94 g,37.8 mmol) in dichloromethane (90 mL). The reaction mixture was stirredat room temperature for 24 h. The reaction mixture was then filteredthrough a pad of Celite®, and the filtration cake was washed withdichloromethane. The combined organic phases were concentrated, and theresulting residue was purified by chromatography on silica gel using50-100% ethyl acetate/hexane as eluant to give the title compound(compound number 609), a compound of this invention, as a pale yellowsolid (5.60 g).

¹H NMR (CDCl₃) δ 9.40 (d, 1H), 8.15 (t, 1H), 7.42 (d, 1H), 7.30 (t, 1H),5.38 (s, 1H), 4.24 (t, 2H), 1.88 (m, 2H), 1.06 (t, 3H).

Step B: Preparation of2-hydroxy-4-oxo-1-propyl-3-[2-(trifluoromethyl)phenyl]-4H-pyrido[1,2-a]-pyrimidiniuminner salt

2-Hydroxy-4-oxo-1-propyl-4H-pyrido[1,2-a]pyrimidinium inner salt (i.e.the product of Step A) (500 mg, 2.45 mmol),1-iodo-2-(trifluoromethyl)benzene (0.34 mL, 2.45 mmol), copper iodide(46.6 mg, 0.245 mmol), 1,10-phenanthroline (44.1 mg, 0.245 mmol) andcesium carbonate (798 mg, 2.45 mmol) were combined inN,N-dimethylformamide (3 mL). The reaction mixture was heated at 118° C.under nitrogen for 24 h. The reaction mixture was cooled andconcentrated, and the resulting residue was purified by reverse phaseliquid chromatography on a XTerra® C18 OBD column (5 micron particle,30×100 mm, manufactured by Waters) using a gradient of 30-90% (1:1acetonitrile/methanol)/water to provide the title compound (compoundnumber 308), a compound of this invention, as a solid (20 mg).

¹H NMR (CDCl₃) δ 9.44 (d, 1H), 8.13 (t, 1H), 7.75 (d, 1H), 7.58 (t, 1H),7.42-7.52 (m, 3H), 7.35 (t, 1H), 4.42-4.35 (m, 1H), 4.24-4.18 (m, 1H),1.80 (q, 2H), 1.05 (t, 3H).

Synthesis Example 8 Preparation of2-hydroxy-3-iodo-1-[[2-(3-methoxyphenyl)-5-thiazolyl]methyl]-4-oxo-4H-pyrido[1,2-a]-pyrimidiniuminner salt Step A: Preparation of1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-3-iodo-4-oxo-4H-pyrido[1,2-a]-pyrimidiniuminner salt

N-iodosuccinimide (2.19 g, 9.76 mmol) was added to a solution of1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidiniuminner salt (i.e. the product of Example 2, Step C) (2.9 g, 9.76 mmol) inN,N-dimethylformamide (30 mL), and the mixture was stirred for 5 min.Water was added, and the mixture was extracted with ethyl acetate. Thecombined organic phases were washed several times with water, dried overNa₂SO₄ and concentrated under reduced pressure. The resulting crudeproduct (compound number 608) (1.2 g), a compound of this invention, wasused in the next step without further purification.

¹H NMR (CD₃COCD₃) δ 9.36 (d, 1H), 8.45 (t, 1H), 8.20 (d, 1H), 7.94 (s,1H), 7.58 (t, 1H), 5.77 (s, 2H).

Step B: Preparation of2-hydroxy-3-iodo-1-[[2-(3-methoxyphenyl)-5-thiazolyl]methyl]-4-oxo-4H-pyrido[1,2-a]-pyrimidiniuminner salt

1-[(2-chloro-5-thiazolyl)methyl]-2-hydroxy-3-iodo-4-oxo-4H-pyrido[1,2-a]-pyrimidiniuminner salt (i.e. the product of Step A) (250 mg, 0.59 mmol),3-methoxybenzeneboronic acid (89 mg, 0.59 mmol) andbis(triphenylphosphine)-palladium(II) dichloride (20 mg, 0.029 mmol)were dissolved in dioxane (3 mL). Aqueous sodium carbonate solution (2N, 1 mL) was added, and the reaction mixture was heated in a microwavereactor for 15 min at 150° C. The cooled reaction mixture was poureddirectly onto a silica gel column and eluted successively with hexanes,30% ethyl acetate in hexanes, 50% ethyl acetate in hexanes, and finallyethyl acetate to yield the title compound (compound number 613), acompound of this invention, as a solid (35 mg).

¹H NMR (CD₃COCD₃) δ 9.38 (d, 1H), 8.43 (t, 1H), 8.20 (d, 1H), 8.13 (s,1H), 7.58 (t, 1H), 7.50 (m, 2H), 7.39 (t, 1H), 7.02 (d, 1H), 5.88 (br s,2H), 3.86 (s, 3H).

Synthesis Example 9 Preparation of2-hydroxy-4-oxo-1-(2,2,2-trifluoroethyl)-3-[2,2,2-trifluoro-1-(methoxyimino)ethyl]-4H-pyrido[1,2-a]-pyrimidiniuminner salt,2-hydroxy-4-oxo-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]-pyrimidiniuminner salt and2-hydroxy-4-oxo-3-(2,2,2-trifluoroacetyl)-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]-pyrimidiniuminner salt Step A: Preparation of2-hydroxy-4-oxo-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]-pyrimidiniuminner salt

A solution of dicyclohexylcarbodiimide (1.0 M in dichloromethane, 108mL, 108 mmol) was added to a solution ofN-(2,2,2-trifluoroethyl)-2-pyridinamine (i.e. the product of Example 5,Step A) (9.51 g, 54.0 mmol) and malonic acid (5.62 g, 54.0 mmol) indichloromethane (190 mL). The reaction mixture was stirred at roomtemperature for 24 h. The reaction mixture was then filtered through apad of Celite®, and the filtration cake washed with dichloromethane. Thecombined organic phases were concentrated under reduced pressure, andthe resulting residue was purified by chromatography on silica gel using50-100% ethyl acetate/hexane as eluant to give the title compound(compound number 610), a compound of this invention, as a pale yellowsolid (7.0 g).

¹H NMR (CD₃S(O)CD₃) δ 9.22 (d, 1H), 8.42 (t, 1H), 8.11 (d, 1H), 7.59 (t,1H), 5.25 (q, 2H), 4.96 (s, 1H).

Step B: Preparation of2-hydroxy-4-oxo-3-(2,2,2-trifluoroacetyl)-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]-pyrimidiniuminner salt

2-Hydroxy-4-oxo-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]-pyrimidiniuminner salt (i.e. the product of Step A) (1.12 g, 4.57 mmol),1,4-diazabicyclo[2.2.2]octane (132.0 mg, 1.12 mmol) and trifluoroaceticanhydride (1.50 mL, 10.92 mmol) were dissolved in1-methyl-2-pyrrolidinone (10 mL), and the reaction mixture was stirredat room temperature for 18 h. The mixture was diluted with ethyl acetate(250 mL), washed with saturated aqueous sodium bicarbonate (150 mL)water (3×100 mL), and concentrated. The residue was triturated withdiethyl ether to yield the title compound (compound number 711), acompound of this invention, as a solid (1.10 g).

¹H NMR (CD₃S(O)CD₃) δ 9.25 (d, 1H), 8.58 (t, 1H), 8.10 (d, 1H), 7.65 (t,1H), 5.25 (q, 2H).

Step C: Preparation of2-hydroxy-4-oxo-1-(2,2,2-trifluoroethyl)-3-[2,2,2-trifluoro-1-(methoxyimino)ethyl]-4H-pyrido[1,2-a]-pyrimidiniuminner salt

A solution of2-hydroxy-4-oxo-3-(2,2,2-trifluoroacetyl)-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]-pyrimidiniuminner salt (i.e. the product of Step B) (75 mg, 0.22 mmol) andmethoxyamine hydrochloride (62 mg, 0.74 mmol) in ethanol (7 mL) wasrefluxed for 3 h. The solvent was concentrated under vacuum, and ethylacetate (60 mL) was added. The organic phase was washed successivelywith a solution of dilute sodium hydroxide (3 mL of 1 N NaOH and 30 mLwater) and water (20 mL). The organic phase was then filtered through aChem Elut™ cartridge (manufactured by Varian) prepacked with Celite® andconcentrated to a crude oil. The resultant residue was purified bypreparative thin layer chromatography on an Analtech Uniplate™ (20×20cm, 2000 microns layer of silica gel) eluted with ethyl acetate toprovide the title compound (compound number 637), a compound of thisinvention, as a thick oil (53 mg, 1:1 mixture of E and Z isomers).

¹H NMR (CDCl₃) δ 9.49 (d, 0.5H), 9.47 (d, 0.5H), 8.23 (t, 1H), 7.61 (d,1H), 7.50 (m, 1H), 5.00 (m, 2H), 4.10 (s, 1.5H), 4.04 (s, 1.5H)

Synthesis Example 10 Preparation of1-[(6-chloro-3-pyridinyl)methyl]-4-hydroxy-2-imino-3-(2-methoxyphenyl)-2H-pyrido[1,2-a]pyrimidiniuminner salt Step A: Preparation of phenyl α-cyano-2-methoxybenzeneacetate

To a slurry of sodium hydride (3.39 g of 60% in mineral oil, 84.9 mmol)in tetrahydrofuran (200 mL) at room temperature was added2-(2-methoxyphenyl)acetonitrile (10.0 g, 67.9 mmol) dropwise. Thereaction mixture was then heated to reflux and the gray suspensionturned dark red over 30 min. Diphenyl carbonate (18.2 g, 84.9 mmol) wasadded portionwise, and the reaction suspension was heated at reflux foran additional 18 h. The reaction mixture was cooled, poured into 1 N HCl(200 mL) and extracted with ethyl acetate (3×200 mL). The organic phaseswere combined, dried over magnesium sulfate, filtered and concentratedonto Celite® under reduced pressure. The resultant residue was purifiedby chromatography on silica gel using 10-90% ethyl acetate/hexane aseluant to give the title compound as a light yellow solid (14.3 g).

¹H NMR (CD₃S(O)CD₃) δ 7.48-7.44 (m, 3H), 7.31 (t, 1H), 7.19-7.03 (m,4H), 6.75 (d, 1H), 5.97 (s, 1H), 3.93 (s, 3H).

Step B: Preparation of1-[(6-chloro-3-pyridinyl)methyl]-4-hydroxy-2-imino-3-(2-methoxyphenyl)-2H-pyrido[1,2-a]pyrimidiniuminner salt

To a solution containing 6-chloro-N-2-pyridinyl-3-pyridinemethanamine(0.82 g, 3.74 mmol) in xylene (100 mL) under nitrogen was added phenylα-cyano-2-methoxybenzeneacetate (i.e. the product of Step A) (1.00 g,3.74 mmol). The reaction mixture was heated to reflux for 24 h. Themixture was cooled, Celite® was added, and the xylene was evaporatedunder reduced pressure. The resultant residue was purified bychromatography on silica gel using a gradient of 100% ethyl acetate to1% triethylamine/40% methanol/59% ethyl acetate as eluant to give thetitle compound (compound number 662), a compound of this invention, as acream solid (4.7 mg). MS (AP+)=393.

¹H NMR (CD₃COCD₃) δ 8.47 (d, 1H), 8.28 (s, 1H), 7.83 (t, 1H), 7.76 (d,1H), 7.38-7.27 (m, 5H), 6.94-6.88 (m, 2H), 5.71 (s, NH), 5.62 (s, 2H),3.64 (s, 3H).

Synthesis Example 11 Preparation of1-[(6-chloro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidiniuminner salt Step A: Preparation ofN-[(6-chloro-3-pyridinyl)methyl]-2-phenyl-N-(2-pyridinyl)malonamic acidethyl ester

2-Phenylmalonic acid monoethyl ester was prepared following theprocedure in Journal of Organic Chemistry 2000, 65, 5834-5836.2-Phenylmalonic acid monoethyl ester (1.02 g, 5.0 mmol) was dissolved inanhydrous dichloromethane (10 mL), and oxalyl chloride (0.52 mL, 6.0mmol) was added, followed by one drop of N,N-dimethylformamide. Thereaction mixture was stirred for 30 min, then concentrated, redissolvedin anhydrous dichloromethane (5 mL) and added to a solution of6-chloro-N-2-pyridinyl-3-pyridinemethanamine (i.e. the product ofExample 3, Step A) (1.1 g, 5.0 mmol) and triethyl amine (0.83 mL, 6.0mmol) in anhydrous dichloromethane (5 mL) at 0° C. The stirred reactionmixture was allowed to warm to room temperature over 30 min. Thereaction mixture was poured onto a silica gel cartridge (Bond Elutemanufactured by Varian) and purified using a gradient of 0-50% ethylacetate/hexanes. A mixture of desired product and starting amine wasisolated (1.3 g of 33 mol % recovered amine/67 mol % desired product).2-Phenylmalonic acid monoethyl ester (0.54 g, 2.6 mmol) was dissolved inanhydrous dichloromethane (3 mL), and oxalyl chloride (0.26 mL, 3.0mmol) was added, followed by one drop of N,N-dimethylformamide. Thereaction mixture was stirred until gas evolution ceased and thenconcentrated, redissolved in anhydrous dichloromethane (3 mL) and addedto the mixture of recovered amine and desired product isolatedpreviously. The reaction mixture was stirred for 30 min and thenconcentrated, and the crude residue was chromatographed as alreadydescribed to give the title compound as a solid (0.9 g).

¹H NMR (CDCl₃) δ 8.50 (m, 1H), 8.18 (s, 1H), 7.60-7.75 (m, 2H), 7.2-7.3(m, 5H), 7.13 (m, 2H), 6.87 (s, 1H), 5.13-4.88 (dd, 2H), 4.86 (s, 1H),4.16 (m, 2H), 1.22 (t, 3H).

Step B: Preparation of1-[(6-chloro-3-pyridinyl)methyl]-2-hydroxy-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidiniuminner salt

N-[(6-chloro-3-pyridinyl)methyl]-2-phenyl-N-(2-pyridinyl)malonamic acidethyl ester (i.e. the product of Step A) (200 mg, 0.49 mmol) was addedto tetralin (0.5 mL) and heated at 200° C. for 30 min. The reactionmixture was cooled and concentrated, and the resulting residue waspurified by chromatography on silica gel using 50-100% ethylacetate/hexane as eluant to give the title compound (compound number59), a compound of this invention, as a solid (15 mg).

¹H NMR (CDCl₃) δ 9.55 (dd, 1H), 8.47 (d, 1H), 8.04 (m, 1H), 7.98 (d,2H), 7.70 (dd, 1H), 7.2-7.4 (m, 6H), 5.58 (s, 2H).

By the procedures described herein together with methods known in theart, the following compounds of Tables 1 to 8 can be prepared.Abbreviations used in Tables 1 to 8 are shown below as X-1 through X-128and Y-1 through Y-71.

Abbreviations X-50 to X-128 pertain to the substituted phenyl ring asshown below. Blank entries in the table denote a hydrogen atom.

R^(a) R^(b) R^(c) R^(d) R^(e) X-50  F X-51  OMe X-52  Cl X-53  F X-54 OMe X-55  Cl X-56  F X-57  OMe X-58  Cl X-59  CF₃ X-60  OCF₃ X-61  SCF₃X-62  SF₅ X-63  Br X-64  cyano X-65  F CF₃ X-66  F OCF₃ X-67  F SCF₃X-68  F Br X-69  S(O)CF₃ X-70  S(O)CF₃ X-71  S(O)CF₃ X-72  Cl cyanoX-73  Cl CF₃ X-74  Cl OCF₃ X-75  Cl SCF₃ X-76  Cl Br X-77  Cl CF₃ X-78 Cl OCF₃ X-79  Cl SCF₃ X-80  Cl Br X-81  Br CF₃ X-82  Br OCF₃ X-83  BrSCF₃ X-84  Br Br X-85  F CF₃ X-86  F OCF₃ X-87  F SCF₃ X-88  F Br X-89 F F F X-90  F F F X-91  F CF₃ X-92  F OCF₃ X-93  F CF₃ X-94  F OCF₃X-95  F F X-96  OCHF₂ X-97  OCHF₂ X-98  OCHF₂ X-99  SCHF₂ X-100 SCHF₂X-101 SCHF₂ X-102 F F X-103 F F X-104 F F X-105 CF₃ CF₃ X-106 F OMeX-107 OMe OMe X-108 F OMe X-109 F OMe X-110 OMe CF₃ X-111 OMe OCF₃ X-112OMe Cl X-113 OMe Br X-114 OMe CF₃ X-115 OMe OCF₃ X-116 OMe Cl X-117 OMeBr X-118 OMe F X-119 OMe OMe X-120 OMe F X-121

X-122

X-123

X-124

X-125

CF₃ X-126 OCHF₂ X-127 OCHF₂ X-128 OCHF₂ methyl Y-1 ethyl Y-2 n-propylY-3 n-butyl Y-4 CHF₂ Y-5 CH₂CH₂CF₃ Y-6 CH₂CH₂CF₂Cl Y-7 isopropyl Y-8s-butyl Y-9 i-butyl Y-10 CH₂CH₂OCH₃ Y-11 CH₂C(O)OCH₃ Y-12 CH₂CH₂SCH₃Y-13 CH₂CH₂S(O)CH₃ Y-14 CH₂CH═CH₂ Y-15 CH₂C≡CH Y-16 cyclopropyl Y-17cyclobutyl Y-18 CH₂CF₃ Y-19 CH(CH₃)CF₃ Y-20 CH₂CF₂CF₃ Y-21CH₂CH₂CHFCF₂Cl Y-22

Y-30

Y-31

Y-32

Y-33

Y-34

Y-35

Y-36

Y-37

Y-38

Y-39

Y-40

Y-41

Y-42

Y-43

Y-44

Y-45

Y-46

Y-47

Y-48

Y-49

Y-50

Y-51

Y-52

Y-53

Y-54

Y-55

Y-56

Y-57

Y-58

Y-59

Y-60

Y-61

Y-62

Y-63

Y-64

Y-65

Y-66

Y-67

Y-68

Y-69

Y-70

Y-71

TABLE 1

R¹ R² is Y-1 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11 X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23 X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35 X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54 X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66 X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78 X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90 X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126X-127 X-128 R² is Y-2 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10 X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22 X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34 X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53 X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65 X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77 X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89 X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125X-126 X-127 X-128 R² is Y-3 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9 X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21 X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33 X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52 X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64 X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76 X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88 X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124X-125 X-126 X-127 X-128 R² is Y-4 X-1  X-2  X-3  X-4  X-5  X-6  X-7 X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19 X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31 X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50 X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62 X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74 X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86 X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98 X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-5 X-1  X-2  X-3  X-4  X-5 X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17 X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29 X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41 X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60 X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72 X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84 X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96 X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-6 X-1  X-2  X-3 X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16 X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28 X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40 X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59 X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71 X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83 X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95 X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-7 X-1 X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14 X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26 X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38 X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57 X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69 X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81 X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93 X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² isY-8 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13 X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25 X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37 X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56 X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68 X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80 X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92 X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128R² is Y-9 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12 X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24 X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36 X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55 X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67 X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79 X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91 X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127X-128 R² is Y-10 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10 X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22 X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34 X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53 X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65 X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77 X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89 X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125X-126 X-127 X-128 R² is Y-11 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8 X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20 X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32 X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51 X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63 X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75 X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87 X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99 X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123X-124 X-125 X-126 X-127 X-128 R² is Y-12 X-1  X-2  X-3  X-4  X-5  X-6 X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18 X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30 X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42 X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61 X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73 X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85 X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97 X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-13 X-1  X-2  X-3  X-4 X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17 X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29 X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41 X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60 X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72 X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84 X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96 X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-14 X-1  X-2 X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15 X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27 X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39 X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58 X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70 X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82 X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94 X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-15X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13 X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25 X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37 X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56 X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68 X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80 X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92 X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128R² is Y-16 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11 X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23 X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35 X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54 X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66 X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78 X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90 X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126X-127 X-128 R² is Y-17 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9 X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21 X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33 X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52 X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64 X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76 X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88 X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124X-125 X-126 X-127 X-128 R² is Y-18 X-1  X-2  X-3  X-4  X-5  X-6  X-7 X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19 X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31 X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50 X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62 X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74 X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86 X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98 X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-19 X-1  X-2  X-3  X-4  X-5 X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17 X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29 X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41 X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60 X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72 X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84 X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96 X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-20 X-1  X-2 X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15 X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27 X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39 X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58 X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70 X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82 X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94 X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-21X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13 X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25 X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37 X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56 X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68 X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80 X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92 X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128R² is Y-22 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11 X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23 X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35 X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54 X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66 X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78 X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90 X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126X-127 X-128 R² is Y-30 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9 X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21 X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33 X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52 X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64 X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76 X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88 X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124X-125 X-126 X-127 X-128 R² is Y-31 X-1  X-2  X-3  X-4  X-5  X-6  X-7 X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19 X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31 X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50 X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62 X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74 X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86 X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98 X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-32 X-1  X-2  X-3  X-4  X-5 X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17 X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29 X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41 X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60 X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72 X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84 X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96 X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-33 X-1  X-2 X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15 X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27 X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39 X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58 X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70 X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82 X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94 X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-34X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13 X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25 X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37 X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56 X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68 X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80 X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92 X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128R² is Y-35 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11 X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23 X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35 X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54 X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66 X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78 X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90 X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126X-127 X-128 R² is Y-36 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9 X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21 X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33 X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52 X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64 X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76 X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88 X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124X-125 X-126 X-127 X-128 R² is Y-37 X-1  X-2  X-3  X-4  X-5  X-6  X-7 X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19 X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31 X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50 X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62 X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74 X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86 X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98 X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-38 X-1  X-2  X-3  X-4  X-5 X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17 X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29 X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41 X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60 X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72 X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84 X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96 X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-39 X-1  X-2 X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15 X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27 X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39 X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58 X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70 X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82 X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94 X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-40X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13 X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25 X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37 X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56 X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68 X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80 X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92 X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128R² is Y-41 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11 X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23 X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35 X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54 X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66 X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78 X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90 X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126X-127 X-128 R² is Y-42 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9 X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21 X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33 X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52 X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64 X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76 X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88 X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124X-125 X-126 X-127 X-128 R² is Y-43 X-1  X-2  X-3  X-4  X-5  X-6  X-7 X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19 X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31 X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50 X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62 X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74 X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86 X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98 X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-44 X-1  X-2  X-3  X-4  X-5 X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17 X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29 X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41 X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60 X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72 X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84 X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96 X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-45 X-1  X-2 X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15 X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27 X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39 X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58 X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70 X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82 X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94 X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-46X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13 X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25 X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37 X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56 X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68 X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80 X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92 X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128R² is Y-47 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11 X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23 X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35 X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54 X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66 X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78 X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90 X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126X-127 X-128 R² is Y-48 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9 X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21 X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33 X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52 X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64 X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76 X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88 X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124X-125 X-126 X-127 X-128 R² is Y-49 X-1  X-2  X-3  X-4  X-5  X-6  X-7 X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19 X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31 X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50 X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62 X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74 X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86 X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98 X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-50 X-1  X-2  X-3  X-4  X-5 X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17 X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29 X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41 X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60 X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72 X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84 X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96 X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-51 X-1  X-2 X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15 X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27 X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39 X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58 X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70 X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82 X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94 X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-52X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13 X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25 X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37 X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56 X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68 X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80 X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92 X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128R² is Y-53 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11 X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23 X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35 X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54 X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66 X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78 X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90 X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126X-127 X-128 R² is Y-54 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9 X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21 X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33 X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52 X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64 X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76 X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88 X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124X-125 X-126 X-127 X-128 R² is Y-55 X-1  X-2  X-3  X-4  X-5  X-6  X-7 X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19 X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31 X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50 X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62 X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74 X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86 X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98 X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-56 X-1  X-2  X-3  X-4  X-5 X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17 X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29 X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41 X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60 X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72 X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84 X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96 X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-57 X-1  X-2 X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15 X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27 X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39 X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58 X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70 X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82 X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94 X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-58X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13 X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25 X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37 X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56 X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68 X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80 X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92 X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128R² is Y-59 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11 X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23 X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35 X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54 X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66 X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78 X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90 X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126X-127 X-128 R² is Y-60 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9 X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21 X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33 X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52 X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64 X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76 X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88 X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124X-125 X-126 X-127 X-128 R² is Y-61 X-1  X-2  X-3  X-4  X-5  X-6  X-7 X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19 X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31 X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50 X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62 X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74 X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86 X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98 X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-62 X-1  X-2  X-3  X-4  X-5 X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17 X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29 X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41 X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60 X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72 X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84 X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96 X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-63 X-1  X-2 X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15 X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27 X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39 X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58 X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70 X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82 X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94 X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-64X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13 X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25 X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37 X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56 X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68 X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80 X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92 X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128R² is Y-65 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11 X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23 X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35 X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54 X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66 X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78 X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90 X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126X-127 X-128 R² is Y-66 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9 X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21 X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33 X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52 X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64 X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76 X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88 X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124X-125 X-126 X-127 X-128 R² is Y-67 X-1  X-2  X-3  X-4  X-5  X-6  X-7 X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19 X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31 X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50 X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62 X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74 X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86 X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98 X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-68 X-1  X-2  X-3  X-4  X-5 X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15  X-16  X-17 X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27  X-28  X-29 X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39  X-40  X-41 X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58  X-59  X-60 X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70  X-71  X-72 X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82  X-83  X-84 X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94  X-95  X-96 X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106 X-107 X-108X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118 X-119 X-120X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-69 X-1  X-2 X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13  X-14  X-15 X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25  X-26  X-27 X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37  X-38  X-39 X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56  X-57  X-58 X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68  X-69  X-70 X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80  X-81  X-82 X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92  X-93  X-94 X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104 X-105 X-106X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116 X-117 X-118X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128 R² is Y-70X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11  X-12  X-13 X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23  X-24  X-25 X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35  X-36  X-37 X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54  X-55  X-56 X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66  X-67  X-68 X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78  X-79  X-80 X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90  X-91  X-92 X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102 X-103 X-104X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114 X-115 X-116X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126 X-127 X-128R² is Y-71 X-1  X-2  X-3  X-4  X-5  X-6  X-7  X-8  X-9  X-10  X-11 X-12  X-13  X-14  X-15  X-16  X-17  X-18  X-19  X-20  X-21  X-22  X-23 X-24  X-25  X-26  X-27  X-28  X-29  X-30  X-31  X-32  X-33  X-34  X-35 X-36  X-37  X-38  X-39  X-40  X-41  X-42  X-50  X-51  X-52  X-53  X-54 X-55  X-56  X-57  X-58  X-59  X-60  X-61  X-62  X-63  X-64  X-65  X-66 X-67  X-68  X-69  X-70  X-71  X-72  X-73  X-74  X-75  X-76  X-77  X-78 X-79  X-80  X-81  X-82  X-83  X-84  X-85  X-86  X-87  X-88  X-89  X-90 X-91  X-92  X-93  X-94  X-95  X-96  X-97  X-98  X-99  X-100 X-101 X-102X-103 X-104 X-105 X-106 X-107 X-108 X-109 X-110 X-111 X-112 X-113 X-114X-115 X-116 X-117 X-118 X-119 X-120 X-121 X-122 X-123 X-124 X-125 X-126X-127 X-128

Table 2

Table 2 is constructed the same as Table 1, except that the chemicalstructure under the Table 1 heading is replaced with the followingstructure:

For example, the first compound in Table 2 is the structure shownimmediately above wherein R¹ is X-1 and R² is Y-1 as defined for Table1.

Table 3

Table 3 is constructed the same as Table 1, except that the chemicalstructure under the Table 1 heading is replaced with the followingstructure:

For example, the first compound in Table 3 is the structure shownimmediately above wherein R¹ is X-1 and R² is Y-1 as defined for Table1.

Table 4

Table 4 is constructed the same as Table 1, except that the chemicalstructure under the Table 1 heading is replaced with the followingstructure:

For example, the first compound in Table 4 is the structure shownimmediately above wherein R¹ is X-1 and R² is Y-1 as defined for Table1.

Table 5

Table 5 is constructed the same as Table 1, except that the chemicalstructure under the Table 1 heading is replaced with the followingstructure:

For example, the first compound in Table 5 is the structure shownimmediately above wherein R¹ is X-1 and R² is Y-1 as defined for Table1.

Table 6

Table 6 is constructed the same as Table 1, except that the chemicalstructure under the Table 1 heading is replaced with the followingstructure:

For example, the first compound in Table 6 is the structure shownimmediately above wherein R¹ is X-1 and R² is Y-1 as defined for Table1.

TABLE 7

R¹ R¹ R¹ R¹ R¹ R¹ R¹ R¹ R¹ R¹ R² is Y-3 X-15 X-17 X-25 X-26 X-27 X-31X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118 X-120 X-121X-122 X-123 X-124 X-125 R² is Y-19 X-15 X-17 X-25 X-26 X-27 X-31 X-35X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118 X-120 X-121 X-122X-123 X-124 X-125 R² is Y-20 X-15 X-17 X-25 X-26 X-27 X-31 X-35 X-50X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78 X-79X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94 X-97X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118 X-120 X-121 X-122 X-123X-124 X-125 R² is Y-22 X-15 X-17 X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102X-103 X-105 X-106 X-107 X-108 X-118 X-120 X-121 X-122 X-123 X-124 X-125R² is Y-30 X-15 X-17 X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102 X-103X-105 X-106 X-107 X-108 X-118 X-120 X-121 X-122 X-123 X-124 X-125 R² isY-31 X-15 X-17 X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102 X-103 X-105X-106 X-107 X-108 X-118 X-120 X-121 X-122 X-123 X-124 X-125 R² is Y-33X-15 X-17 X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56X-57 X-59 X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85X-86 X-87 X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102 X-103 X-105 X-106X-107 X-108 X-118 X-120 X-121 X-122 X-123 X-124 X-125 R² is Y-34 X-15X-17 X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57X-59 X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86X-87 X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107X-108 X-118 X-120 X-121 X-122 X-123 X-124 X-125 R² is Y-36 X-15 X-17X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108X-118 X-120 X-121 X-122 X-123 X-124 X-125 R² is Y-37 X-15 X-17 X-25 X-26X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89X-90 X-93 X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118X-120 X-121 X-122 X-123 X-124 X-125 R² is Y-38 X-15 X-17 X-25 X-26 X-27X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90X-93 X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118 X-120X-121 X-122 X-123 X-124 X-125 R² is Y-39 X-15 X-17 X-25 X-26 X-27 X-31X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118 X-120 X-121X-122 X-123 X-124 X-125 R² is Y-40 X-15 X-17 X-25 X-26 X-27 X-31 X-35X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118 X-120 X-121 X-122X-123 X-124 X-125 R² is Y-45 X-15 X-17 X-25 X-26 X-27 X-31 X-35 X-50X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78 X-79X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94 X-97X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118 X-120 X-121 X-122 X-123X-124 X-125 R² is Y-49 X-15 X-17 X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102X-103 X-105 X-106 X-107 X-108 X-118 X-120 X-121 X-122 X-123 X-124 X-125R² is Y-52 X-15 X-17 X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102 X-103X-105 X-106 X-107 X-108 X-118 X-120 X-121 X-122 X-123 X-124 X-125 R² isY-53 X-15 X-17 X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102 X-103 X-105X-106 X-107 X-108 X-118 X-120 X-121 X-122 X-123 X-124 X-125 R² is Y-55X-15 X-17 X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56X-57 X-59 X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85X-86 X-87 X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102 X-103 X-105 X-106X-107 X-108 X-118 X-120 X-121 X-122 X-123 X-124 X-125 R² is Y-64 X-15X-17 X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57X-59 X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86X-87 X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107X-108 X-118 X-120 X-121 X-122 X-123 X-124 X-125 R² is Y-65 X-15 X-17X-25 X-26 X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59X-60 X-61 X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87X-88 X-89 X-90 X-93 X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108X-118 X-120 X-121 X-122 X-123 X-124 X-125 R² is Y-66 X-15 X-17 X-25 X-26X-27 X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61X-63 X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89X-90 X-93 X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118X-120 X-121 X-122 X-123 X-124 X-125 R² is Y-67 X-15 X-17 X-25 X-26 X-27X-31 X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63X-77 X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90X-93 X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118 X-120X-121 X-122 X-123 X-124 X-125 R² is Y-68 X-15 X-17 X-25 X-26 X-27 X-31X-35 X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77X-78 X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93X-94 X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118 X-120 X-121X-122 X-123 X-124 X-125 R² is Y-69 X-15 X-17 X-25 X-26 X-27 X-31 X-35X-50 X-51 X-52 X-53 X-54 X-55 X-56 X-57 X-59 X-60 X-61 X-63 X-77 X-78X-79 X-80 X-81 X-82 X-83 X-84 X-85 X-86 X-87 X-88 X-89 X-90 X-93 X-94X-97 X-100 X-102 X-103 X-105 X-106 X-107 X-108 X-118 X-120 X-121 X-122X-123 X-124 X-125

Table 8

Table 8 is constructed the same as Table 7, except that the chemicalstructure under the Table 7 heading is replaced with the followingstructure:

For example, the first compound in Table 8 is the structure shownimmediately above wherein R¹ is X-15 and R² is Y-3 as defined for Table7.

A compound of this invention will generally be used as an invertebratepest control active ingredient in a composition, i.e. formulation, withat least one additional component selected from the group consisting ofsurfactants, solid diluents and liquid diluents, which serves as acarrier. The formulation or composition ingredients are selected to beconsistent with the physical properties of the active ingredient, modeof application and environmental factors such as soil type, moisture andtemperature.

Useful formulations include both liquid and solid compositions. Liquidcompositions include solutions (including emulsifiable concentrates),suspensions, emulsions (including microemulsions and/or suspoemulsions)and the like, which optionally can be thickened into gels. The generaltypes of aqueous liquid compositions are soluble concentrate, suspensionconcentrate, capsule suspension, concentrated emulsion, microemulsionand suspo-emulsion. The general types of nonaqueous liquid compositionsare emulsifiable concentrate, microemulsifiable concentrate, dispersibleconcentrate and oil dispersion.

The general types of solid compositions are dusts, powders, granules,pellets, prills, pastilles, tablets, filled films (including seedcoatings) and the like, which can be water-dispersible (“wettable”) orwater-soluble. Films and coatings formed from film-forming solutions orflowable suspensions are particularly useful for seed treatment. Activeingredient can be (micro)encapsulated and further formed into asuspension or solid formulation; alternatively the entire formulation ofactive ingredient can be encapsulated (or “overcoated”). Encapsulationcan control or delay release of the active ingredient. An emulsifiablegranule combines the advantages of both an emulsifiable concentrateformulation and a dry granular formulation. High-strength compositionsare primarily used as intermediates for further formulation.

Sprayable formulations are typically extended in a suitable mediumbefore spraying. Such liquid and solid formulations are formulated to bereadily diluted in the spray medium, usually water. Spray volumes canrange from about from about one to several thousand liters per hectare,but more typically are in the range from about ten to several hundredliters per hectare. Sprayable formulations can be tank mixed with wateror another suitable medium for foliar treatment by aerial or groundapplication, or for application to the growing medium of the plant.Liquid and dry formulations can be metered directly into drip irrigationsystems or metered into the furrow during planting. Liquid and solidformulations can be applied onto seeds of crops and other desirablevegetation as seed treatments before planting to protect developingroots and other subterranean plant parts and/or foliage through systemicuptake.

The formulations will typically contain effective amounts of activeingredient, diluent and surfactant within the following approximateranges which add up to 100 percent by weight.

Weight Percent Active Ingredient Diluent Surfactant Water-Dispersibleand Water- 0.001-90 0-99.999 0-15 soluble Granules, Tablets and PowdersOil Dispersions, Suspensions,    1-50 40-99    0-50 Emulsions, Solutions(including Emulsifiable Concentrates) Dusts    1-25 70-99    0-5 Granules and Pellets 0.001-95 5-99.999 0-15 High Strength Compositions  90-99 0-10    0-2 

Solid diluents include, for example, clays such as bentonite,montmorillonite, attapulgite and kaolin, gypsum, cellulose, titaniumdioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose),silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodiumcarbonate and bicarbonate, and sodium sulfate. Typical solid diluentsare described in Watkins et al., Handbook of Insecticide Dust Diluentsand Carriers, 2nd Ed., Dorland Books, Caldwell, N.J.

Liquid diluents include, for example, water, N,N-dimethylalkanamides(e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide,N-alkylpyrrolidones (e.g., N-methylpyrrolidinone), ethylene glycol,triethylene glycol, propylene glycol, dipropylene glycol, polypropyleneglycol, propylene carbonate, butylene carbonate, paraffins (e.g., whitemineral oils, normal paraffins, isoparaffins), alkylbenzenes,alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin,aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes,alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone,isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamylacetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate,tridecyl acetate and isobornyl acetate, other esters such as alkylatedlactate esters, dibasic esters and γ-butyrolactone, and alcohols, whichcan be linear, branched, saturated or unsaturated, such as methanol,ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol,n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol,isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleylalcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol andbenzyl alcohol. Liquid diluents also include glycerol esters ofsaturated and unsaturated fatty acids (typically C₆-C₂₂), such as plantseed and fruit oils (e.g, oils of olive, castor, linseed, sesame, corn(maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean,rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beeftallow, pork tallow, lard, cod liver oil, fish oil), and mixturesthereof. Liquid diluents also include alkylated fatty acids (e.g.,methylated, ethylated, butylated) wherein the fatty acids can beobtained by hydrolysis of glycerol esters from plant and animal sources,and can be purified by distillation. Typical liquid diluents aredescribed in Marsden, Solvents Guide, 2nd Ed., Interscience, New York,1950.

The solid and liquid compositions of the present invention often includeone or more surfactants. When added to a liquid, surfactants (also knownas “surface-active agents”) generally modify, most often reduce, thesurface tension of the liquid. Depending on the nature of thehydrophilic and lipophilic groups in a surfactant molecule, surfactantscan be useful as wetting agents, dispersants, emulsifiers or defoamingagents.

Surfactants can be classified as nonionic, anionic or cationic. Nonionicsurfactants useful for the present compositions include, but are notlimited to: alcohol alkoxylates such as alcohol alkoxylates based onnatural and synthetic alcohols (which are branched or linear) andprepared from the alcohols and ethylene oxide, propylene oxide, butyleneoxide or mixtures thereof; amine ethoxylates, alkanolamides andethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylatedsoybean, castor and rapeseed oils; alkylphenol alkoxylates such asoctylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenolethoxylates and dodecyl phenol ethoxylates (prepared from the phenolsand ethylene oxide, propylene oxide, butylene oxide or mixturesthereof); block polymers prepared from ethylene oxide or propylene oxideand reverse block polymers where the terminal blocks are prepared frompropylene oxide; ethoxylated fatty acids; ethoxylated fatty esters andoils; ethoxylated methyl esters; ethoxylated tristyrylphenol (includingthose prepared from ethylene oxide, propylene oxide, butylene oxide ormixtures thereof); fatty acid esters, glycerol esters, lanolin-basedderivatives, polyethoxylate esters such as polyethoxylated sorbitanfatty acid esters, polyethoxylated sorbitol fatty acid esters andpolyethoxylated glycerol fatty acid esters; other sorbitan derivativessuch as sorbitan esters; polymeric surfactants such as randomcopolymers, block copolymers, alkyd peg (polyethylene glycol) resins,graft or comb polymers and star polymers; polyethylene glycols (pegs);polyethylene glycol fatty acid esters; silicone-based surfactants; andsugar-derivatives such as sucrose esters, alkyl polyglycosides and alkylpolysaccharides.

Useful anionic surfactants include, but are not limited to: alkylarylsulfonic acids and their salts; carboxylated alcohol or alkylphenolethoxylates; diphenyl sulfonate derivatives; lignin and ligninderivatives such as lignosulfonates; maleic or succinic acids or theiranhydrides; olefin sulfonates; phosphate esters such as phosphate estersof alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates andphosphate esters of styryl phenol ethoxylates; protein-basedsurfactants; sarcosine derivatives; styryl phenol ether sulfate;sulfates and sulfonates of oils and fatty acids; sulfates and sulfonatesof ethoxylated alkylphenols; sulfates of alcohols; sulfates ofethoxylated alcohols; sulfonates of amines and amides such asN,N-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, anddodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes;sulfonates of naphthalene and alkyl naphthalene; sulfonates offractionated petroleum; sulfosuccinamates; and sulfosuccinates and theirderivatives such as dialkyl sulfosuccinate salts.

Useful cationic surfactants include, but are not limited to: amides andethoxylated amides; amines such as N-alkyl propanediamines,tripropylenetriamines and dipropylenetetramines, and ethoxylated amines,ethoxylated diamines and propoxylated amines (prepared from the aminesand ethylene oxide, propylene oxide, butylene oxide or mixturesthereof); amine salts such as amine acetates and diamine salts;quaternary ammonium salts such as quaternary salts, ethoxylatedquaternary salts and diquaternary salts; and amine oxides such asalkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.

Also useful for the present compositions are mixtures of nonionic andanionic surfactants or mixtures of nonionic and cationic surfactants.Nonionic, anionic and cationic surfactants and their recommended usesare disclosed in a variety of published references includingMcCutcheon's Emulsifiers and Detergents, annual American andInternational Editions published by McCutcheon's Division, TheManufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopediaof Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; andA. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition,John Wiley and Sons, New York, 1987.

Compositions of this invention can also contain formulation auxiliariesand additives, known to those skilled in the art as formulation aids(some of which can be considered to also function as solid diluents,liquid diluents or surfactants). Such formulation auxiliaries andadditives can control: pH (buffers), foaming during processing(antifoams such polyorganosiloxanes), sedimentation of activeingredients (suspending agents), viscosity (thixotropic thickeners),in-container microbial growth (antimicrobials), product freezing(antifreezes), color (dyes/pigment dispersions), wash-off (film formersor stickers), evaporation (evaporation retardants), and otherformulation attributes. Film formers include, for example, polyvinylacetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinylacetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers andwaxes. Examples of formulation auxiliaries and additives include thoselisted in McCutcheon's Volume 2: Functional Materials, annualInternational and North American editions published by McCutcheon'sDivision, The Manufacturing Confectioner Publishing Co.; and PCTPublication WO 03/024222.

The compound of Formula 1 and any other active ingredients are typicallyincorporated into the present compositions by dissolving the activeingredient in a solvent or by grinding in a liquid or dry diluent.Solutions, including emulsifiable concentrates, can be prepared bysimply mixing the ingredients. If the solvent of a liquid compositionintended for use as an emulsifiable concentrate is water-immiscible, anemulsifier is typically added to emulsify the active-containing solventupon dilution with water. Active ingredient slurries, with particlediameters of up to 2,000 μm can be wet milled using media mills toobtain particles with average diameters below 3 μm. Aqueous slurries canbe made into finished suspension concentrates (see, for example, U.S.Pat. No. 3,060,084) or further processed by spray drying to formwater-dispersible granules. Dry formulations usually require dry millingprocesses, which produce average particle diameters in the 2 to 10 μmrange. Dusts and powders can be prepared by blending and usuallygrinding (such as with a hammer mill or fluid-energy mill). Granules andpellets can be prepared by spraying the active material upon preformedgranular carriers or by agglomeration techniques. See Browning,“Agglomeration”, Chemical Engineering, Dec. 4, 1967, pp 147-48, Perry'sChemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963,pages 8-57 and following, and WO 91/13546. Pellets can be prepared asdescribed in U.S. Pat. No. 4,172,714. Water-dispersible andwater-soluble granules can be prepared as taught in U.S. Pat. No.4,144,050, U.S. Pat. No. 3,920,442 and DE 3,246,493. Tablets can beprepared as taught in U.S. Pat. No. 5,180,587, U.S. Pat. No. 5,232,701and U.S. Pat. No. 5,208,030. Films can be prepared as taught in GB2,095,558 and U.S. Pat. No. 3,299,566.

For further information regarding the art of formulation, see T. S.Woods, “The Formulator's Toolbox—Product Forms for Modern Agriculture”in Pesticide Chemistry and Bioscience, The Food-Environment Challenge,T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th InternationalCongress on Pesticide Chemistry, The Royal Society of Chemistry,Cambridge, 1999, pp. 120-133. See also U.S. Pat. No. 3,235,361, Col. 6,line 16 through Col. 7, line 19 and Examples 10-41; U.S. Pat. No.3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12,15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182;U.S. Pat. No. 2,891,855, Col. 3, line 66 through Col. 5, line 17 andExamples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons,Inc., New York, 1961, pp 81-96; Hance et al., Weed Control Handbook, 8thEd., Blackwell Scientific Publications, Oxford, 1989; and Developmentsin formulation technology, PJB Publications, Richmond, UK, 2000.

In the following Examples, all formulations are prepared in conventionalways. Compound numbers refer to compounds in Index Tables A-F. Withoutfurther elaboration, it is believed that one skilled in the art usingthe preceding description can utilize the present invention to itsfullest extent. The following Examples are, therefore, to be construedas merely illustrative, and not limiting of the disclosure in any waywhatsoever. Percentages are by weight except where otherwise indicated.

Example A High Strength Concentrate

Compound 7 98.5% silica aerogel 0.5% synthetic amorphous fine silica1.0%

Example B Wettable Powder

Compound 50 65.0% dodecylphenol polyethylene glycol ether 2.0% sodiumligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite(calcined) 23.0%

Example C Granule

Compound 138 10.0% attapulgite granules (low volatile matter, 90.0%0.71/0.30 mm; U.S.S. No. 25-50 sieves)

Example D Extruded Pellet

Compound 157 25.0% anhydrous sodium sulfate 10.0% crude calciumligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0%calcium/magnesium bentonite 59.0%

Example E Emulsifiable Concentrate

Compound 7 10.0% polyoxyethylene sorbitol hexoleate 20.0% C₆-C₁₀ fattyacid methyl ester 70.0%

Example F Microemulsion

Compound 50 5.0% polyvinylpyrrolidone-vinyl acetate copolymer 30.0%alkylpolyglycoside 30.0% glyceryl monooleate 15.0% water 20.0%

Example G Seed Treatment

Compound 138 20.00% polyvinylpyrrolidone-vinyl acetate copolymer 5.00%montan acid wax 5.00% calcium ligninsulfonate 1.00%polyoxyethylene/polyoxypropylene block copolymers 1.00% stearyl alcohol(POE 20) 2.00% polyorganosilane 0.20% colorant red dye 0.05% water65.75%

Example H Fertilizer Stick

Compound 157 2.50% pyrrolidone-styrene copolymer 4.80% tristyrylphenyl16-ethoxylate 2.30% talc 0.80% corn starch 5.00% Nitrophoska ® Permanent15-9-15 slow-release fertilizer 36.00% (BASF) kaolin 38.00% water 10.60%

Compounds of this invention exhibit activity against a wide spectrum ofinvertebrate pests. These pests include invertebrates inhabiting avariety of environments such as, for example, plant foliage, roots,soil, harvested crops or other foodstuffs, building structures or animalinteguments. These pests include, for example, invertebrates feeding onfoliage (including leaves, stems, flowers and fruits), seeds, wood,textile fibers or animal blood or tissues, and thereby causing injury ordamage to, for example, growing or stored agronomic crops, forests,greenhouse crops, ornamentals, nursery crops, stored foodstuffs or fiberproducts, or houses or other structures or their contents, or beingharmful to animal health or public health. Those skilled in the art willappreciate that not all compounds are equally effective against allgrowth stages of all pests.

These present compounds and compositions are thus useful agronomicallyfor protecting field crops from phytophagous invertebrate pests, andalso nonagronomically for protecting other horticultural crops andplants from phytophagous invertebrate pests. This utility includesprotecting crops and other plants (i.e. both agronomic and nonagronomic)that contain genetic material introduced by genetic engineering (i.e.transgenic) or modified by mutagenesis to provide advantageous traits.Examples of such traits include tolerance to herbicides, resistance tophytophagous pests (e.g., insects, mites, aphids, spiders, nematodes,snails, plant-pathogenic fungi, bacteria and viruses), improved plantgrowth, increased tolerance of adverse growing conditions such as highor low temperatures, low or high soil moisture, and high salinity,increased flowering or fruiting, greater harvest yields, more rapidmaturation, higher quality and/or nutritional value of the harvestedproduct, or improved storage or process properties of the harvestedproducts. Transgenic plants can be modified to express multiple traits.Examples of plants containing traits provided by genetic engineering ormutagenesis include varieties of corn, cotton, soybean and potatoexpressing an insecticidal Bacillus thuringiensis toxin such as YIELDGARD®, KNOCKOUT®, STARLINK®, BOLLGARD®, NuCOTN® and NEWLEAF®, andherbicide-tolerant varieties of corn, cotton, soybean and rapeseed suchas ROUNDUP READY®, LIBERTY LINK®, IMI®, STS® and CLEARFIELD®, as well ascrops expressing N-acetyltransferase (GAT) to provide resistance toglyphosate herbicide, or crops containing the HRA gene providingresistance to herbicides inhibiting acetolactate synthase (ALS). Thepresent compounds and compositions may interact synergistically withtraits introduced by genetic engineering or modified by mutagenesis,thus enhancing phenotypic expression or effectiveness of the traits orincreasing the invertebrate pest control effectiveness of the presentcompounds and compositions. In particular, the present compounds andcompositions may interact synergistically with the phenotypic expressionof proteins or other natural products toxic to invertebrate pests toprovide greater-than-additive control of these pests.

Compositions of this invention can also optionally comprise plantnutrients, e.g., a fertilizer composition comprising at least one plantnutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium,magnesium, iron, copper, boron, manganese, zinc, and molybdenum. Of noteare compositions comprising at least one fertilizer compositioncomprising at least one plant nutrient selected from nitrogen,phosphorus, potassium, sulfur, calcium and magnesium. Compositions ofthe present invention which further comprise at least one plant nutrientcan be in the form of liquids or solids. Of note are solid formulationsin the form of granules, small sticks or tablets. Solid formulationscomprising a fertilizer composition can be prepared by mixing thecompound or composition of the present invention with the fertilizercomposition together with formulating ingredients and then preparing theformulation by methods such as granulation or extrusion. Alternativelysolid formulations can be prepared by spraying a solution or suspensionof a compound or composition of the present invention in a volatilesolvent onto a previous prepared fertilizer composition in the form ofdimensionally stable mixtures, e.g., granules, small sticks or tablets,and then evaporating the solvent.

Examples of agronomic or nonagronomic invertebrate pests include eggs,larvae and adults of the order Lepidoptera, such as armyworms, cutworms,loopers, and heliothines in the family Noctuidae (e.g., pink stem borer(Sesamia inferens Walker), corn stalk borer (Sesamia nonagrioidesLefebvre), southern armyworm (Spodoptera eridania Cramer), fall armyworm(Spodoptera fugiperda J. E. Smith), beet armyworm (Spodoptera exiguaHübner), cotton leafworm (Spodoptera littoralis Boisduval),yellowstriped armyworm (Spodoptera ornithogalli Guenée), black cutworm(Agrotis ipsilon Hufnagel), velvetbean caterpillar (Anticarsiagemmatalis Hübner), green fruitworm (Lithophane antennata Walker),cabbage armyworm (Barathra brassicae Linnaeus), soybean looper(Pseudoplusia includens Walker), cabbage looper (Trichoplusia niHübner), tobacco budworm (Heliothis virescens Fabricius)); borers,casebearers, webworms, coneworms, cabbageworms and skeletonizers fromthe family Pyralidae (e.g., European corn borer (Ostrinia nubilalisHübner), navel orangeworm (Amyelois transitella Walker), corn rootwebworm (Crambus caliginosellus Clemens), sod webworms (Pyralidae:Crambinae) such as sod worm (Herpetogramma licarsisalis Walker),sugarcane stem borer (Chilo infuscatellus Snellen), tomato small borer(Neoleucinodes elegantalis Guenée), green leafroller (Cnaphalocerusmedinalis), grape leaffolder (Desmia funeralis Hübner), melon worm(Diaphania nitidalis Stoll), cabbage center grub (Helluala hydralisGuenée), yellow stem borer (Scirpophaga incertulas Walker), early shootborer (Scirpophaga infuscatellus Snellen), white stem borer (Scirpophagainnotata Walker), top shoot borer (Scirpophaga nivella Fabricius),dark-headed rice borer (Chilo polychrysus Meyrick), cabbage clustercaterpillar (Crocidolomia binotalis English)); leafrollers, budworms,seed worms, and fruit worms in the family Tortricidae (e.g., codlingmoth (Cydia pomonella Linnaeus), grape berry moth (Endopiza viteanaClemens), oriental fruit moth (Grapholita molesta Busck), citrus falsecodling moth (Cryptophlebia leucotreta Meyrick), citrus borer(Ecdytolopha aurantiana Lima), redbanded leafroller (Argyrotaeniavelutinana Walker), obliquebanded leafroller (Choristoneura rosaceanaHarris), light brown apple moth (Epiphyas postvittana Walker), Europeangrape berry moth (Eupoecilia ambiguella Hübner), apple bud moth(Pandemis pyrusana Kearfott), omnivorous leafroller (Platynota stultanaWalsingham), barred fruit-tree tortrix (Pandemis cerasana Hübner), applebrown tortrix (Pandemis heparana Denis & Schiffermüller)); and manyother economically important lepidoptera (e.g., diamondback moth(Plutella xylostella Linnaeus), pink bollworm (Pectinophora gossypiellaSaunders), gypsy moth (Lymantria dispar Linnaeus), peach fruit borer(Carposina niponensis Walsingham), peach twig borer (Anarsia lineatellaZeller), potato tuberworm (Phthorimaea operculella Zeller), spottedteniform leafminer (Lithocolletis blancardella Fabricius), Asiatic appleleafminer (Lithocolletis ringoniella Matsumura), rice leaffolder(Lerodea eufala Edwards), apple leafminer (Leucoptera scitella Zeller));eggs, nymphs and adults of the order Blattodea including cockroachesfrom the families Blattellidae and Blattidae (e.g., oriental cockroach(Blatta orientalis Linnaeus), Asian cockroach (Blatella asahinaiMizukubo), German cockroach (Blattella germanica Linnaeus), brownbandedcockroach (Supella longipalpa Fabricius), American cockroach(Periplaneta americana Linnaeus), brown cockroach (Periplaneta brunneaBurmeister), Madeira cockroach (Leucophaea maderae Fabricius)), smokybrown cockroach (Periplaneta fuliginosa Service), Australian Cockroach(Periplaneta australasiae Fabr.), lobster cockroach (Nauphoeta cinereaOlivier) and smooth cockroach (Symploce pallens Stephens)); eggs, foliarfeeding, fruit feeding, root feeding, seed feeding and vesicular tissuefeeding larvae and adults of the order Coleoptera including weevils fromthe families Anthribidae, Bruchidae, and Curculionidae (e.g., bollweevil (Anthonomus grandis Boheman), rice water weevil (Lissorhoptrusoryzophilus Kuschel), granary weevil (Sitophilus granarius Linnaeus),rice weevil (Sitophilus oryzae Linnaeus)), annual bluegrass weevil(Listronotus maculicollis Dietz), bluegrass billbug (Sphenophorusparvulus Gyllenhal), hunting billbug (Sphenophorus venatus vestitus),Denver billbug (Sphenophorus cicatristriatus Fahraeus)); flea beetles,cucumber beetles, rootworms, leaf beetles, potato beetles, andleafminers in the family Chrysomelidae (e.g., Colorado potato beetle(Leptinotarsa decemlineata Say), western corn rootworm (Diabroticavirgifera virgifera LeConte)); chafers and other beetles from the familyScarabaeidae (e.g., Japanese beetle (Popillia japonica Newman), orientalbeetle (Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse)Baraud), northern masked chafer (Cyclocephala borealis Arrow), southernmasked chafer (Cyclocephala immaculata Olivier or C. lurida Bland), dungbeetle and white grub (Aphodius spp.), black turfgrass ataenius(Ataenius spretulus Haldeman), green June beetle (Cotinis nitidaLinnaeus), Asiatic garden beetle (Maladera castanea Arrow), May/Junebeetles (Phyllophaga spp.) and European chafer (Rhizotrogus majalisRazoumowsky)); carpet beetles from the family Dermestidae; wirewormsfrom the family Elateridae; bark beetles from the family Scolytidae andflour beetles from the family Tenebrionidae. In addition, agronomic andnonagronomic pests include: eggs, adults and larvae of the orderDermaptera including earwigs from the family Forficulidae (e.g.,European earwig (Forficula auricularia Linnaeus), black earwig(Chelisoches morio Fabricius)); eggs, immatures, adults and nymphs ofthe orders Hemiptera and Homoptera such as, plant bugs from the familyMiridae, cicadas from the family Cicadidae, leafhoppers (e.g. Empoascaspp.) from the family Cicadellidae, bed bugs (e.g., Cimex lectulariusLinnaeus) from the family Cimicidae, planthoppers from the familiesFulgoroidae and Delphacidae, treehoppers from the family Membracidae,psyllids from the family Psyllidae, whiteflies from the familyAleyrodidae, aphids from the family Aphididae, phylloxera from thefamily Phylloxeridae, mealybugs from the family Pseudococcidae, scalesfrom the families Coccidae, Diaspididae and Margarodidae, lace bugs fromthe family Tingidae, stink bugs from the family Pentatomidae, chinchbugs (e.g., hairy chinch bug (Blissus leucopterus hirtus Montandon) andsouthern chinch bug (Blissus insularis Barber)) and other seed bugs fromthe family Lygaeidae, spittlebugs from the family Cercopidae squash bugsfrom the family Coreidae, and red bugs and cotton stainers from thefamily Pyrrhocoridae. Also included are eggs, larvae, nymphs and adultsof the order Acari (mites) such as spider mites and red mites in thefamily Tetranychidae (e.g., European red mite (Panonychus ulmi Koch),two spotted spider mite (Tetranychus urticae Koch), McDaniel mite(Tetranychus mcdanieli McGregor)); flat mites in the familyTenuipalpidae (e.g., citrus flat mite (Brevipalpus lewisi McGregor));rust and bud mites in the family Eriophyidae and other foliar feedingmites and mites important in human and animal health, i.e. dust mites inthe family Epidermoptidae, follicle mites in the family Demodicidae,grain mites in the family Glycyphagidae; ticks in the family Ixodidae,commonly known as hard ticks (e.g., deer tick (Ixodes scapularis Say),Australian paralysis tick (Ixodes holocyclus Neumann), American dog tick(Dermacentor variabilis Say), lone star tick (Amblyomma americanumLinnaeus)) and ticks in the family Argasidae, commonly known as softticks (e.g., relapsing fever tick (Ornithodoros turicata), common fowltick (Argas radiatus)); scab and itch mites in the families Psoroptidae,Pyemotidae, and Sarcoptidae; eggs, adults and immatures of the orderOrthoptera including grasshoppers, locusts and crickets (e.g., migratorygrasshoppers (e.g., Melanoplus sanguinipes Fabricius, M. differentialisThomas), American grasshoppers (e.g., Schistocerca americana Drury),desert locust (Schistocerca gregaria Forskal), migratory locust (Locustamigratoria Linnaeus), bush locust (Zonocerus spp.), house cricket(Acheta domesticus Linnaeus), mole crickets (e.g., tawny mole cricket(Scapteriscus vicinus Scudder) and southern mole cricket (Scapteriscusborellii Giglio-Tos)); eggs, adults and immatures of the order Dipteraincluding leafminers (e.g., Liriomyza spp. such as serpentine vegetableleafminer (Liriomyza sativae Blanchard)), midges, fruit flies(Tephritidae), frit flies (e.g., Oscinella fit Linnaeus), soil maggots,house flies (e.g., Musca domestica Linnaeus), lesser house flies (e.g.,Fannia canicularis Linnaeus, F. femoralis Stein), stable flies (e.g.,Stomoxys calcitrans Linnaeus), face flies, horn flies, blow flies (e.g.,Chrysomya spp., Phormia spp.), and other muscoid fly pests, horse flies(e.g., Tabanus spp.), bot flies (e.g., Gastrophilus spp., Oestrus spp.),cattle grubs (e.g., Hypoderma spp.), deer flies (e.g., Chrysops spp.),keds (e.g., Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes(e.g., Aedes spp., Anopheles spp., Culex spp.), black flies (e.g.,Prosimulium spp., Simulium spp.), biting midges, sand flies, sciarids,and other Nematocera; eggs, adults and immatures of the orderThysanoptera including onion thrips (Thrips tabaci Lindeman), flowerthrips (Frankliniella spp.), and other foliar feeding thrips; insectpests of the order Hymenoptera including ants of the Family Formicidaeincluding the Florida carpenter ant (Camponotus floridanus Buckley), redcarpenter ant (Camponotus ferrugineus Fabricius), black carpenter ant(Camponotus pennsylvanicus De Geer), white-footed ant (Technomyrmexalbipes fr. Smith), big headed ants (Pheidole sp.), ghost ant (Tapinomamelanocephalum Fabricius); Pharaoh ant (Monomorium pharaonis Linnaeus),little fire ant (Wasmannia auropunctata Roger), fire ant (Solenopsisgeminata Fabricius), red imported fire ant (Solenopsis invicta Buren),Argentine ant (Iridomyrmex humilis Mayr), crazy ant (Paratrechinalongicornis Latreille), pavement ant (Tetramorium caespitum Linnaeus),cornfield ant (Lasius alienus Förster) and odorous house ant (Tapinomasessile Say). Other Hymenoptera including bees (including carpenterbees), hornets, yellow jackets, wasps, and sawflies (Neodiprion spp.;Cephus spp.); insect pests of the order Isoptera including termites inthe Termitidae (e.g., Macrotermes sp., Odontotermes obesus Rambur),Kalotermitidae (e.g., Cryptotermes sp.), and Rhinotermitidae (e.g.,Reticulitermes sp., Coptotermes sp., Heterotermes tenuis Hagen)families, the eastern subterranean termite (Reticulitermes flavipesKollar), western subterranean termite (Reticulitermes hesperus Banks),Formosan subterranean termite (Coptotermes formosanus Shiraki), WestIndian drywood termite (Incisitermes immigrans Snyder), powder posttermite (Cryptotermes brevis Walker), drywood termite (Incisitermessnyderi Light), southeastern subterranean termite (Reticulitermesvirginicus Banks), western drywood termite (Incisitermes minor Hagen),arboreal termites such as Nasutitermes sp. and other termites ofeconomic importance; insect pests of the order Thysanura such assilverfish (Lepisma saccharina Linnaeus) and firebrat (Thermobiadomestica Packard); insect pests of the order Mallophaga and includingthe head louse (Pediculus humanus capitis De Geer), body louse(Pediculus humanus Linnaeus), chicken body louse (Menacanthus stramineusNitszch), dog biting louse (Trichodectes canis De Geer), fluff louse(Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank),short-nosed cattle louse (Haematopinus eurysternus Nitzsch), long-nosedcattle louse (Linognathus vituli Linnaeus) and other sucking and chewingparasitic lice that attack man and animals; insect pests of the orderSiphonoptera including the oriental rat flea (Xenopsylla cheopisRothschild), cat flea (Ctenocephalides felis Bouche), dog flea(Ctenocephalides canis Curtis), hen flea (Ceratophyllus gallinaeSchrank), sticktight flea (Echidnophaga gallinacea Westwood), human flea(Pulex irritans Linnaeus) and other fleas afflicting mammals and birds.Additional arthropod pests covered include: spiders in the order Araneaesuch as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik)and the black widow spider (Latrodectus mactans Fabricius), andcentipedes in the order Scutigeromorpha such as the house centipede(Scutigera coleoptrata Linnaeus). Compounds of the present inventionalso have activity on members of the Classes Nematoda, Cestoda,Trematoda, and Acanthocephala including economically important membersof the orders Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida,and Enoplida such as but not limited to economically importantagricultural pests (i.e. root knot nematodes in the genus Meloidogyne,lesion nematodes in the genus Pratylenchus, stubby root nematodes in thegenus Trichodorus, etc.) and animal and human health pests (i.e. alleconomically important flukes, tapeworms, and roundworms, such asStrongylus vulgaris in horses, Toxocara canis in dogs, Haemonchuscontortus in sheep, Dirofilaria immitis Leidy in dogs, Anoplocephalaperfoliata in horses, Fasciola hepatica Linnaeus in ruminants, etc.).

Compounds of the invention show particularly high activity against pestsin the order Lepidoptera (e.g., Alabama argillacea Hübner (cotton leafworm), Archips argyrospila Walker (fruit tree leaf roller), A. rosanaLinnaeus (European leaf roller) and other Archips species, Chilosuppressalis Walker (rice stem borer), Cnaphalocrosis medinalis Guenée(rice leaf roller), Crambus caliginosellus Clemens (corn root webworm),Crambus teterrellus Zincken (bluegrass webworm), Cydia pomonellaLinnaeus (codling moth), Earias insulana Boisduval (spiny bollworm),Earias vittella Fabricius (spotted bollworm), Helicoverpa armigeraHübner (American bollworm), Helicoverpa zea Boddie (corn earworm),Heliothis virescens Fabricius (tobacco budworm), Herpetogrammalicarsisalis Walker (sod webworm), Lobesia botrana Denis &Schiffermüller (grape berry moth), Pectinophora gossypiella Saunders(pink bollworm), Phyllocnistis citrella Stainton (citrus leafminer),Pieris brassicae Linnaeus (large white butterfly), Pieris rapae Linnaeus(small white butterfly), Plutella xylostella Linnaeus (diamondbackmoth), Spodoptera exigua Hübner (beet armyworm), Spodoptera lituraFabricius (tobacco cutworm, cluster caterpillar), Spodoptera frugiperdaJ. E. Smith (fall armyworm), Trichoplusia ni Hübner (cabbage looper) andTuta absoluta Meyrick (tomato leafminer)).

Compounds of the invention also have significant activity on membersfrom the order Homoptera including: Acyrthosiphon pisum Harris (peaaphid), Aphis craccivora Koch (cowpea aphid), Aphis fabae Scopoli (blackbean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphispomi De Geer (apple aphid), Aphis spiraecola Patch (spirea aphid),Aulacorthum solani Kaltenbach (foxglove aphid), Chaetosiphon fragaefoliiCockerell (strawberry aphid), Diuraphis noxia Kurdjumov/Mordvilko(Russian wheat aphid), Dysaphis plantaginea Paaserini (rosy appleaphid), Eriosoma lanigerum Hausmann (woolly apple aphid), Hyalopteruspruni Geoffroy (mealy plum aphid), Lipaphis erysimi Kaltenbach (turnipaphid), Metopolophium dirrhodum Walker (cereal aphid), Macrosiphumeuphorbiae Thomas (potato aphid), Myzus persicae Sulzer (peach-potatoaphid, green peach aphid), Nasonovia ribisnigri Mosley (lettuce aphid),Pemphigus spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch(corn leaf aphid), Rhopalosiphum padi Linnaeus (bird cherry-oat aphid),Schizaphis graminum Rondani (greenbug), Sitobion avenae Fabricius(English grain aphid), Therioaphis maculata Buckton (spotted alfalfaaphid), Toxoptera aurantii Boyer de Fonscolombe (black citrus aphid),and Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges spp.(adelgids); Phylloxera devastatrix Pergande (pecan phylloxera); Bemisiatabaci Gennadius (tobacco whitefly, sweetpotato whitefly), Bemisiaargentifolii Bellows & Perring (silverleaf whitefly), Dialeurodes citriAshmead (citrus whitefly) and Trialeurodes vaporariorum Westwood(greenhouse whitefly); Empoasca fabae Harris (potato leafhopper),Laodelphax striatellus Fallen (smaller brown planthopper), Macrolestesquadrilineatus Forbes (aster leafhopper), Nephotettix cinticeps Uhler(green leafhopper), Nephotettix nigropictus Stål (rice leafhopper),Nilaparvata lugens Stål (brown planthopper), Peregrinus maidis Ashmead(corn planthopper), Sogatella furcifera Horvath (white-backedplanthopper), Sogatodes orizicola Muir (rice delphacid), Typhlocybapomaria McAtee white apple leafhopper, Erythroneoura spp. (grapeleafhoppers); Magicidada septendecim Linnaeus (periodical cicada);Icerya purchasi Maskell (cottony cushion scale), Quadraspidiotusperniciosus Comstock (San Jose scale); Planococcus citri Risso (citrusmealybug); Pseudococcus spp. (other mealybug complex); Cacopsyllapyricola Foerster (pear psylla), Trioza diospyri Ashmead (persimmonpsylla).

Compounds of this invention may also have activity on members from theorder Hemiptera including: Acrosternum hilare Say (green stink bug),Anasa tristis De Geer (squash bug), Blissus leucopterus leucopterus Say(chinch bug), Cimex lectularius Linnaeus (bed bug) Corythuca gossypiiFabricius (cotton lace bug), Cyrtopeltis modesta Distant (tomato bug),Dysdercus suturellus Herrich-Schäffer (cotton stainer), Euchistus servusSay (brown stink bug), Euchistus variolarius Palisot de Beauvois(one-spotted stink bug), Graptosthetus spp. (complex of seed bugs),Leptoglossus corculus Say (leaf-footed pine seed bug), Lygus lineolarisPalisot de Beauvois (tarnished plant bug), Nezara viridula Linnaeus(southern green stink bug), Oebalus pugnax Fabricius (rice stink bug),Oncopeltus fasciatus Dallas (large milkweed bug), Pseudatomoscelisseriatus Reuter (cotton fleahopper). Other insect orders controlled bycompounds of the invention include Thysanoptera (e.g., Frankliniellaoccidentalis Pergande (western flower thrips), Scirthothrips citriMoulton (citrus thrips), Sericothrips variabilis Beach (soybean thrips),and Thrips tabaci Lindeman (onion thrips); and the order Coleoptera(e.g., Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachnavarivestis Mulsant (Mexican bean beetle) and wireworms of the generaAgriotes, Athous or Limonius).

Note that some contemporary classification systems place Homoptera as asuborder within the order Hemiptera.

Of note is use of compounds of this invention for controlling potatoleafhopper (Empoasca fabae). Of note is use of compounds of thisinvention for controlling corn planthopper (Peregrinus maidis). Of noteis use of compounds of this invention for controlling cotton melon aphid(Aphis gossypii). Of note is use of compounds of this invention forcontrolling green peach aphid (Myzus persicae). Of note is use ofcompounds of this invention for controlling diamondback moth (Plutellaxylostella). Of note is use of compounds of this invention forcontrolling fall armyworm (Spodoptera frugiperda).

Of note is use of compounds of this invention for controlling southerngreen stink bug (Nezara viridula), western tarnished plant bug (Lygushesperus), rice water weevil (Lissorhoptrus oryzophilus), rice brownplanthopper (Nilaparvata lugens), rice green leafhopper (Nephotettixvirescens) and striped rice borer (Chilo suppressalis).

Compounds of this invention can also be mixed with one or more otherbiologically active compounds or agents including insecticides,fungicides, nematocides, bactericides, acaricides, herbicides, herbicidesafeners, growth regulators such as insect molting inhibitors androoting stimulants, chemosterilants, semiochemicals, repellents,attractants, pheromones, feeding stimulants, other biologically activecompounds or entomopathogenic bacteria, virus or fungi to form amulti-component pesticide giving an even broader spectrum of agronomicand nonagronomic utility. Thus the present invention also pertains to acomposition comprising a biologically effective amount of a compound ofFormula 1, at least one additional component selected from the groupconsisting of surfactants, solid diluents and liquid diluents, and atleast one additional biologically active compound or agent. For mixturesof the present invention, the other biologically active compounds oragents can be formulated together with the present compounds, includingthe compounds of Formula 1, to form a premix, or the other biologicallyactive compounds or agents can be formulated separately from the presentcompounds, including the compounds of Formula 1, and the twoformulations combined together before application (e.g., in a spraytank) or, alternatively, applied in succession.

Examples of such biologically active compounds or agents with whichcompounds of this invention can be formulated are insecticides such asabamectin, acephate, acequinocyl, acetamiprid, acrinathrin, amidoflumet,amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin,bifenazate, bistrifluoron, borate,3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide(cyantraniliprole), buprofezin, cadusafos, carbaryl, carbofuran, cartap,carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos,chlorpyrifos-methyl, chromafenozide, clofentezin, clothianidin,cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin,gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin,zeta-cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon,dieldrin, diflubenzuron, dimefluthrin, dimehypo, dimethoate,dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate,ethiprole, etofenprox, etoxazole, fenbutatin oxide, fenothiocarb,fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid,flubendiamide, flucythrinate, flufenerim, flufenoxuron, fluvalinate,tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide,hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb,insecticidal soaps, isofenphos, lufenuron, malathion, metaflumizone,metaldehyde, methamidophos, methidathion, methiodicarb, methomyl,methoprene, methoxychlor, metofluthrin, monocrotophos, methoxyfenozide,nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion,parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon,pirimicarb, profenofos, profluthrin, propargite, protrifenbute,pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl,pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine,spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat,sulprofos, sulfoxaflor, tebufenozide, tebufenpyrad, teflubenzuron,tefluthrin, terbufos, tetrachlorvinphos, tetramethrin, thiacloprid,thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin,triazamate, trichlorfon, triflumuron, Bacillus thuringiensisdelta-endotoxins, entomopathogenic bacteria, entomopathogenic virusesand entomopathogenic fungi.

Of note are insecticides such as abamectin, acetamiprid, acrinathrin,amitraz, avermectin, azadirachtin, bifenthrin,3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide(cyantraniliprole), buprofezin, cadusafos, carbaryl, cartap,chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin,cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin,lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin,cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin,endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole,fenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid,flubendiamide, flufenoxuron, fluvalinate, formetanate, fosthiazate,hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron,metaflumizone, methiodicarb, methomyl, methoprene, methoxyfenozide,nitenpyram, nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin,pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad,spirodiclofen, spiromesifen, spirotetramat, tebufenozide, tetramethrin,thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin,triazamate, triflumuron, Bacillus thuringiensis delta-endotoxins, allstrains of Bacillus thuringiensis and all strains of Nucleo polyhydrosisviruses.

One embodiment of biological agents for mixing with compounds of thisinvention include entomopathogenic bacteria such as Bacillusthuringiensis, and the encapsulated delta-endotoxins of Bacillusthuringiensis such as MVP® and MVPII® bioinsecticides prepared by theCellCap® process (CellCap®, MVP® and MVPII® are trademarks of MycogenCorporation, Indianapolis, Ind., USA); entomopathogenic fungi such asgreen muscardine fungus; and entomopathogenic (both naturally occurringand genetically modified) viruses including baculovirus, nucleopolyhedrovirus (NPV) such as Helicoverpa zea nucleopolyhedrovirus (HzNPV),Anagrapha falcifera nucleopolyhedrovirus (AfNPV); and granulosis virus(GV) such as Cydia pomonella granulosis virus (CpGV).

Of particular note is such a combination where the other invertebratepest control active ingredient belongs to a different chemical class orhas a different site of action than the compound of Formula 1. Incertain instances, a combination with at least one other invertebratepest control active ingredient having a similar spectrum of control buta different site of action will be particularly advantageous forresistance management. Thus, a composition of the present invention canfurther comprise a biologically effective amount of at least oneadditional invertebrate pest control active ingredient having a similarspectrum of control but belonging to a different chemical class orhaving a different site of action. These additional biologically activecompounds or agents include, but are not limited to, sodium channelmodulators such as bifenthrin, cypermethrin, cyhalothrin,lambda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin,dimefluthrin, esfenvalerate, fenvalerate, indoxacarb, metofluthrin,profluthrin, pyrethrin and tralomethrin; cholinesterase inhibitors suchas chlorpyrifos, methomyl, oxamyl, thiodicarb and triazamate;neonicotinoids such as acetamiprid, clothianidin, dinotefuran,imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam;insecticidal macrocyclic lactones such as spinetoram, spinosad,abamectin, avermectin and emamectin; GABA (γ-aminobutyric acid)-gatedchloride channel antagonists such as avermectin or blockers such asethiprole and fipronil; chitin synthesis inhibitors such as buprofezin,cyromazine, flufenoxuron, hexaflumuron, lufenuron, novaluron,noviflumuron and triflumuron; juvenile hormone mimics such asdiofenolan, fenoxycarb, methoprene and pyriproxyfen; octopamine receptorligands such as amitraz; molting inhibitors and ecdysone agonists suchas azadirachtin, methoxyfenozide and tebufenozide; ryanodine receptorligands such as ryanodine, anthranilic diamides such aschlorantraniliprole (see U.S. Pat. No. 6,747,047, PCT Publications WO2003/015518 and WO 2004/067528) and flubendiamide (see U.S. Pat. No.6,603,044); nereistoxin analogs such as cartap; mitochondrial electrontransport inhibitors such as chlorfenapyr, hydramethylnon and pyridaben;lipid biosynthesis inhibitors such as spirodiclofen and spiromesifen;cyclodiene insecticides such as dieldrin or endosulfan; pyrethroids;carbamates; insecticidal ureas; and biological agents includingnucleopolyhedro viruses (NPV), members of Bacillus thuringiensis,encapsulated delta-endotoxins of Bacillus thuringiensis, and othernaturally occurring or genetically modified insecticidal viruses.

Further examples of biologically active compounds or agents with whichcompounds of this invention can be formulated are: fungicides such asacibenzolar, aldimorph, amisulbrom, azaconazole, azoxystrobin,benalaxyl, benomyl, benthiavalicarb, benthiavalicarb-isopropyl,binomial, biphenyl, bitertanol, blasticidin-S, Bordeaux mixture(Tribasic copper sulfate), boscalid/nicobifen, bromuconazole,bupirimate, buthiobate, carboxin, carpropamid, captafol, captan,carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole,copper oxychloride, copper salts such as copper sulfate and copperhydroxide, cyazofamid, cyflunamid, cymoxanil, cyproconazole, cyprodinil,dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb,difenoconazole, dimethomorph, dimoxystrobin, diniconazole,diniconazole-M, dinocap, discostrobin, dithianon, dodemorph, dodine,econazole, etaconazole, edifenphos, epoxiconazole, ethaboxam, ethirimol,ethridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole,fencaramid, fenfuram, fenhexamide, fenoxanil, fenpiclonil, fenpropidin,fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferfurazoate,ferimzone, fluazinam, fludioxonil, flumetover, fluopicolide,fluoxastrobin, fluquinconazole, fluquinconazole, flusilazole,flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminum,fuberidazole, furalaxyl, furametapyr, hexaconazole, hymexazole,guazatine, imazalil, imibenconazole, iminoctadine, iodicarb, ipconazole,iprobenfos, iprodione, iprovalicarb, isoconazole, isoprothiolane,kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, maneb,mapanipyrin, mefenoxam, mepronil, metalaxyl, metconazole,methasulfocarb, metiram, metominostrobin/fenominostrobin, mepanipyrim,metrafenone, miconazole, myclobutanil, neo-asozin (ferricmethanearsonate), nuarimol, octhilinone, ofurace, orysastrobin,oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, paclobutrazol,penconazole, pencycuron, penthiopyrad, perfurazoate, phosphonic acid,phthalide, picobenzamid, picoxystrobin, polyoxin, probenazole,prochloraz, procymidone, propamocarb, propamocarb-hydrochloride,propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin,pryazophos, pyrifenox, pyrimethanil, pyrifenox, pyrolnitrine,pyroquilon, quinconazole, quinoxyfen, quintozene, silthiofam,simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole,techrazene, tecloftalam, tecnazene, tetraconazole, thiabendazole,thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil,tolclofos-methyl, tolyfluanid, triadimefon, triadimenol, triarimol,triazoxide, tridemorph, trimoprhamide tricyclazole, trifloxystrobin,triforine, triticonazole, uniconazole, validamycin, vinclozolin, zineb,ziram, and zoxamide; nematocides such as aldicarb, imicyafos, oxamyl andfenamiphos; bactericides such as streptomycin; acaricides such asamitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol,dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin,fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad.

In certain instances, combinations of a compound of this invention withother biologically active (particularly invertebrate pest control)compounds or agents (i.e. active ingredients) can result in agreater-than-additive (i.e. synergistic) effect. Reducing the quantityof active ingredients released in the environment while ensuringeffective pest control is always desirable. When synergism ofinvertebrate pest control active ingredients occurs at application ratesgiving agronomically satisfactory levels of invertebrate pest control,such combinations can be advantageous for reducing crop production costand decreasing environmental load.

Compounds of this invention and compositions thereof can be applied toplants genetically transformed to express proteins toxic to invertebratepests (such as Bacillus thuringiensis delta-endotoxins). Such anapplication may provide a broader spectrum of plant protection and beadvantageous for resistance management. The effect of the exogenouslyapplied invertebrate pest control compounds of this invention may besynergistic with the expressed toxin proteins.

General references for these agricultural protectants (i.e.insecticides, fungicides, nematocides, acaricides, herbicides andbiological agents) include The Pesticide Manual, 13th Edition, C. D. S.Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K.,2003 and The BioPesticide Manual, 2^(nd) Edition, L. G. Copping, Ed.,British Crop Protection Council, Farnham, Surrey, U.K., 2001.

For embodiments where one or more of these various mixing partners areused, the weight ratio of these various mixing partners (in total) tothe compound of Formula 1 is typically between about 1:3000 and about3000:1. Of note are weight ratios between about 1:300 and about 300:1(for example ratios between about 1:30 and about 30:1). One skilled inthe art can easily determine through simple experimentation thebiologically effective amounts of active ingredients necessary for thedesired spectrum of biological activity. It will be evident thatincluding these additional components can expand the spectrum ofinvertebrate pests controlled beyond the spectrum controlled by thecompound of Formula 1 alone.

Table A lists specific combinations of a compound of Formula 1 withother invertebrate pest control agents illustrative of the mixtures,compositions and methods of the present invention. The first column ofTable A lists the specific invertebrate pest control agents (e.g.,“Abamectin” in the first line). The second column of Table A lists themode of action (if known) or chemical class of the invertebrate pestcontrol agents. The third column of Table A lists embodiment(s) ofranges of weight ratios for rates at which the invertebrate pest controlagent can be applied relative to a compound of Formula 1 (e.g., “50:1 to1:50” of abamectin relative to a compound of Formula 1 by weight). Thus,for example, the first line of Table A specifically discloses thecombination of a compound of Formula 1 with abamectin can be applied ina weight ratio between 50:1 to 1:50. The remaining lines of Table A areto be construed similarly. Of further note Table A lists specificcombinations of a compound of Formula 1 with other invertebrate pestcontrol agents illustrative of the mixtures, compositions and methods ofthe present invention and includes additional embodiments of weightratio ranges for application rates.

TABLE A Invertebrate Pest Mode of Action or Typical Control AgentChemical Class Weight Ratio Abamectin macrocyclic lactones 50:1 to 1:50Acetamiprid neonicotinoids 150:1 to 1:200 Amitraz octopamine receptorligands 200:1 to 1:100 Avermectin macrocyclic lactones 50:1 to 1:50Azadirachtin ecdysone agonists 100:1 to 1:120 Beta-cyfluthrin sodiumchannel modulators 150:1 to 1:200 Bifenthrin sodium channel modulators100:1 to 1:10  Buprofezin chitin synthesis inhibitors 500:1 to 1:50 Cartap nereistoxin analogs 100:1 to 1:200 Chlorantraniliprole ryanodinereceptor ligands 100:1 to 1:120 Chlorfenapyr mitochondrial electron300:1 to 1:200 transport inhibitors Chlorpyrifos cholinesteraseinhibitors 500:1 to 1:200 Clothianidin neonicotinoids 100:1 to 1:400Cyfluthrin sodium channel modulators 150:1 to 1:200 Cyhalothrin sodiumchannel modulators 150:1 to 1:200 Cypermethrin sodium channel modulators150:1 to 1:200 Cyromazine chitin synthesis inhibitors 400:1 to 1:50 Deltamethrin sodium channel modulators  50:1 to 1:400 Dieldrincyclodiene insecticides 200:1 to 1:100 Dinotefuran neonicotinoids 150:1to 1:200 Diofenolan molting inhibitor 150:1 to 1:200 Emamectinmacrocyclic lactones 50:1 to 1:10 Endosulfan cyclodiene insecticides200:1 to 1:100 Esfenvalerate sodium channel modulators 100:1 to 1:400Ethiprole GABA-regulated chloride 200:1 to 1:100 channel blockersFenothiocarb 150:1 to 1:200 Fenoxycarb juvenile hormone mimics 500:1 to1:100 Fenvalerate sodium channel modulators 150:1 to 1:200 FipronilGABA-regulated chloride 150:1 to 1:100 channel blockers Flonicamid 200:1to 1:100 Flubendiamide ryanodine receptor ligands 100:1 to 1:120Flufenoxuron chitin synthesis inhibitors 200:1 to 1:100 Hexaflumuronchitin synthesis inhibitors 300:1 to 1:50  Hydramethylnon mitochondrialelectron 150:1 to 1:250 transport inhibitors Imidacloprid neonicotinoids1000:1 to 1:1000 Indoxacarb sodium channel modulators 200:1 to 1:50 Lambda-cyhalothrin sodium channel modulators  50:1 to 1:250 Lufenuronchitin synthesis inhibitors 500:1 to 1:250 Metaflumizone 200:1 to 1:200Methomyl cholinesterase inhibitors 500:1 to 1:100 Methoprene juvenilehormone mimics 500:1 to 1:100 Methoxyfenozide ecdysone agonists 50:1 to1:50 Nitenpyram neonicotinoids 150:1 to 1:200 Nithiazine neonicotinoids150:1 to 1:200 Novaluron chitin synthesis inhibitors 500:1 to 1:150Oxamyl cholinesterase inhibitors 200:1 to 1:200 Pymetrozine 200:1 to1:100 Pyrethrin sodium channel modulators 100:1 to 1:10  Pyridabenmitochondrial electron 200:1 to 1:100 transport inhibitors Pyridalyl200:1 to 1:100 Pyriproxyfen juvenile hormone mimics 500:1 to 1:100Ryanodine ryanodine receptor ligands 100:1 to 1:120 Spinetorammacrocyclic lactones 150:1 to 1:100 Spinosad macrocyclic lactones 500:1to 1:10  Spirodiclofen lipid biosynthesis inhibitors 200:1 to 1:200Spiromesifen lipid biosynthesis inhibitors 200:1 to 1:200 Tebufenozideecdysone agonists 500:1 to 1:250 Thiacloprid neonicotinoids 100:1 to1:200 Thiamethoxam neonicotinoids 1250:1 to 1:1000 Thiodicarbcholinesterase inhibitors 500:1 to 1:400 Thiosultap-sodium 150:1 to1:100 Tralomethrin sodium channel modulators 150:1 to 1:200 Triazamatecholinesterase inhibitors 250:1 to 1:100 Triflumuron chitin synthesisinhibitors 200:1 to 1:100 Bacillus thuringiensis biological agents 50:1to 1:10 Bacillus thuringiensis biological agents 50:1 to 1:10delta-endotoxin NPV (e.g., Gemstar) biological agents 50:1 to 1:10 (a)ryanodine receptor ligands 100:1 to 1:120 (a)3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]-phenyl]-1H-pyrazole-5-carboxamide(cyantraniliprole)

Of note is the composition of the present invention wherein the at leastone additional biologically active compound or agent is selected fromthe Invertebrate Pest Control Agents listed in Table A above.

The weight ratios of a compound, including a compound of Formula 1, tothe additional invertebrate pest control agent typically are between1000:1 and 1:1000, with one embodiment being between 500:1 and 1:500,another embodiment being between 250:1 and 1:200 and another embodimentbeing between 100:1 and 1:50.

Listed below in Table B are embodiments of specific compositionscomprising a compound of Formula 1 (compound numbers refer to compoundsin Index Tables A-I) and an additional invertebrate pest control agent.

TABLE B Mixture Comp. Invertebrate Pest Control No. No. and Agent A-1 7and Abamectin A-2 7 and Acetamiprid A-3 7 and Amitraz A-4 7 andAvermectin A-5 7 and Azadirachtin A-6 7 and Beta-cyfluthrin A-7 7 andBifenthrin A-8 7 and Buprofezin A-9 7 and Cartap A-10 7 andChlorantraniliprole A-11 7 and Chlorfenapyr A-12 7 and Chlorpyrifos A-137 and Clothianidin A-14 7 and Cyfluthrin A-15 7 and Cyhalothrin A-16 7and Cypermethrin A-17 7 and Cyromazine A-18 7 and Deltamethrin A-19 7and Dieldrin A-20 7 and Dinotefuran A-21 7 and Diofenolan A-22 7 andEmamectin A-23 7 and Endosulfan A-24 7 and Esfenvalerate A-25 7 andEthiprole A-26 7 and Fenothiocarb A-27 7 and Fenoxycarb A-28 7 andFenvalerate A-29 7 and Fipronil A-30 7 and Flonicamid A-31 7 andFlubendiamide A-32 7 and Flufenoxuron A-33 7 and Hexaflumuron A-34 7 andHydramethylnon A-35 7 and Imidacloprid A-36 7 and Indoxacarb A-37 7 andLambda-cyhalothrin A-38 7 and Lufenuron A-39 7 and Metaflumizone A-40 7and Methomyl A-41 7 and Methoprene A-42 7 and Methoxyfenozide A-43 7 andNitenpyram A-44 7 and Nithiazine A-45 7 and Novaluron A-46 7 and OxamylA-47 7 and Pymetrozine A-48 7 and Pyrethrin A-49 7 and Pyridaben A-50 7and Pyridalyl A-51 7 and Pyriproxyfen A-52 7 and Ryanodine A-53 7 andSpinetoram A-54 7 and Spinosad A-55 7 and Spirodiclofen A-56 7 andSpiromesifen A-57 7 and Tebufenozide A-58 7 and Thiacloprid A-59 7 andThiamethoxam A-60 7 and Thiodicarb A-61 7 and Thiosultap-sodium A-62 7and Tralomethrin A-63 7 and Triazamate A-64 7 and Triflumuron A-65 7 andBacillus thuringiensis A-66 7 and Bacillus thuringiensis delta-endotoxinA-67 7 and NPV (e.g., Gemstar) A-68 7 and (a) B-1 50 and Abamectin B-250 and Acetamiprid B-3 50 and Amitraz B-4 50 and Avermectin B-5 50 andAzadirachtin B-6 50 and Beta-cyfluthrin B-7 50 and Bifenthrin B-8 50 andBuprofezin B-9 50 and Cartap B-10 50 and Chlorantraniliprole B-11 50 andChlorfenapyr B-12 50 and Chlorpyrifos B-13 50 and Clothianidin B-14 50and Cyfluthrin B-15 50 and Cyhalothrin B-16 50 and Cypermethrin B-17 50and Cyromazine B-18 50 and Deltamethrin B-19 50 and Dieldrin B-20 50 andDinotefuran B-21 50 and Diofenolan B-22 50 and Emamectin B-23 50 andEndosulfan B-24 50 and Esfenvalerate B-25 50 and Ethiprole B-26 50 andFenothiocarb B-27 50 and Fenoxycarb B-28 50 and Fenvalerate B-29 50 andFipronil B-30 50 and Flonicamid B-31 50 and Flubendiamide B-32 50 andFlufenoxuron B-33 50 and Hexaflumuron B-34 50 and Hydramethylnon B-35 50and Imidacloprid B-36 50 and Indoxacarb B-37 50 and Lambda-cyhalothrinB-38 50 and Lufenuron B-39 50 and Metaflumizone B-40 50 and MethomylB-41 50 and Methoprene B-42 50 and Methoxyfenozide B-43 50 andNitenpyram B-44 50 and Nithiazine B-45 50 and Novaluron B-46 50 andOxamyl B-47 50 and Pymetrozine B-48 50 and Pyrethrin B-49 50 andPyridaben B-50 50 and Pyridalyl B-51 50 and Pyriproxyfen B-52 50 andRyanodine B-53 50 and Spinetoram B-54 50 and Spinosad B-55 50 andSpirodiclofen B-56 50 and Spiromesifen B-57 50 and Tebufenozide B-58 50and Thiacloprid B-59 50 and Thiamethoxam B-60 50 and Thiodicarb B-61 50and Thiosultap-sodium B-62 50 and Tralomethrin B-63 50 and TriazamateB-64 50 and Triflumuron B-65 50 and Bacillus thuringiensis B-66 50 andBacillus thuringiensis delta-endotoxin B-67 50 and NPV (e.g., Gemstar)B-68 50 and (a) C-1 138 and Abamectin C-2 138 and Acetamiprid C-3 138and Amitraz C-4 138 and Avermectin C-5 138 and Azadirachtin C-6 138 andBeta-cyfluthrin C-7 138 and Bifenthrin C-8 138 and Buprofezin C-9 138and Cartap C-10 138 and Chlorantraniliprole C-11 138 and ChlorfenapyrC-12 138 and Chlorpyrifos C-13 138 and Clothianidin C-14 138 andCyfluthrin C-15 138 and Cyhalothrin C-16 138 and Cypermethrin C-17 138and Cyromazine C-18 138 and Deltamethrin C-19 138 and Dieldrin C-20 138and Dinotefuran C-21 138 and Diofenolan C-22 138 and Emamectin C-23 138and Endosulfan C-24 138 and Esfenvalerate C-25 138 and Ethiprole C-26138 and Fenothiocarb C-27 138 and Fenoxycarb C-28 138 and FenvalerateC-29 138 and Fipronil C-30 138 and Flonicamid C-31 138 and FlubendiamideC-32 138 and Flufenoxuron C-33 138 and Hexaflumuron C-34 138 andHydramethylnon C-35 138 and Imidacloprid C-36 138 and Indoxacarb C-37138 and Lambda-cyhalothrin C-38 138 and Lufenuron C-39 138 andMetaflumizone C-40 138 and Methomyl C-41 138 and Methoprene C-42 138 andMethoxyfenozide C-43 138 and Nitenpyram C-44 138 and Nithiazine C-45 138and Novaluron C-46 138 and Oxamyl C-47 138 and Pymetrozine C-48 138 andPyrethrin C-49 138 and Pyridaben C-50 138 and Pyridalyl C-51 138 andPyriproxyfen C-52 138 and Ryanodine C-53 138 and Spinetoram C-54 138 andSpinosad C-55 138 and Spirodiclofen C-56 138 and Spiromesifen C-57 138and Tebufenozide C-58 138 and Thiacloprid C-59 138 and Thiamethoxam C-60138 and Thiodicarb C-61 138 and Thiosultap-sodium C-62 138 andTralomethrin C-63 138 and Triazamate C-64 138 and Triflumuron C-65 138and Bacillus thuringiensis C-66 138 and Bacillus thuringiensisdelta-endotoxin C-67 138 and NPV (e.g., Gemstar) C-68 138 And (a) D-1157 and Abamectin D-2 157 and Acetamiprid D-3 157 and Amitraz D-4 157and Avermectin D-5 157 and Azadirachtin D-6 157 and Beta-cyfluthrin D-7157 and Bifenthrin D-8 157 and Buprofezin D-9 157 and Cartap D-10 157and Chlorantraniliprole D-11 157 and Chlorfenapyr D-12 157 andChlorpyrifos D-13 157 and Clothianidin D-14 157 and Cyfluthrin D-15 157and Cyhalothrin D-16 157 and Cypermethrin D-17 157 and Cyromazine D-18157 and Deltamethrin D-19 157 and Dieldrin D-20 157 and Dinotefuran D-21157 and Diofenolan D-22 157 and Emamectin D-23 157 and Endosulfan D-24157 and Esfenvalerate D-25 157 and Ethiprole D-26 157 and FenothiocarbD-27 157 and Fenoxycarb D-28 157 and Fenvalerate D-29 157 and FipronilD-30 157 and Flonicamid D-31 157 and Flubendiamide D-32 157 andFlufenoxuron D-33 157 and Hexaflumuron D-34 157 and Hydramethylnon D-35157 and Imidacloprid D-36 157 and Indoxacarb D-37 157 andLambda-cyhalothrin D-38 157 and Lufenuron D-39 157 and MetaflumizoneD-40 157 and Methomyl D-41 157 and Methoprene D-42 157 andMethoxyfenozide D-43 157 and Nitenpyram D-44 157 and Nithiazine D-45 157and Novaluron D-46 157 and Oxamyl D-47 157 and Pymetrozine D-48 157 andPyrethrin D-49 157 and Pyridaben D-50 157 and Pyridalyl D-51 157 andPyriproxyfen D-52 157 and Ryanodine D-53 157 and Spinetoram D-54 157 andSpinosad D-55 157 and Spirodiclofen D-56 157 and Spiromesifen D-57 157and Tebufenozide D-58 157 and Thiacloprid D-59 157 and Thiamethoxam D-60157 and Thiodicarb D-61 157 and Thiosultap-sodium D-62 157 andTralomethrin D-63 157 and Triazamate D-64 157 and Triflumuron D-65 157and Bacillus thuringiensis D-66 157 and Bacillus thuringiensisdelta-endotoxin D-67 157 and NPV (e.g., Gemstar) D-68 157 And (a) (a)3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide(cyantraniliprole)

The specific mixtures listed in Table B typically combine a compound ofFormula 1 with the other invertebrate pest agent in the ratios specifiedin Table A.

Invertebrate pests are controlled in agronomic and nonagronomicapplications by applying one or more compounds of this invention,typically in the form of a composition, in a biologically effectiveamount, to the environment of the pests, including the agronomic and/ornonagronomic locus of infestation, to the area to be protected, ordirectly on the pests to be controlled.

Thus the present invention comprises a method for controlling aninvertebrate pest in agronomic and/or nonagronomic applications,comprising contacting the invertebrate pest or its environment with abiologically effective amount of one or more of the compounds of theinvention, or with a composition comprising at least one such compoundor a composition comprising at least one such compound and abiologically effective amount of at least one additional biologicallyactive compound or agent. Examples of suitable compositions comprising acompound of the invention and a biologically effective amount of atleast one additional biologically active compound or agent includegranular compositions wherein the additional active compound is presenton the same granule as the compound of the invention or on granulesseparate from those of the compound of the invention.

To achieve contact with a compound or composition of the invention toprotect a field crop from invertebrate pests, the compound orcomposition is typically applied to the seed of the crop beforeplanting, to the foliage (e.g., leaves, stems, flowers, fruits) of cropplants, or to the soil or other growth medium before or after the cropis planted.

One embodiment of a method of contact is by spraying. Alternatively, agranular composition comprising a compound of the invention can beapplied to the plant foliage or the soil. Compounds of this inventioncan also be effectively delivered through plant uptake by contacting theplant with a composition comprising a compound of this invention appliedas a soil drench of a liquid formulation, a granular formulation to thesoil, a nursery box treatment or a dip of transplants. Of note is acomposition of the present invention in the form of a soil drench liquidformulation. Also of note is a method for controlling an invertebratepest comprising contacting the invertebrate pest or its environment witha biologically effective amount of a compound of the present inventionor with a composition comprising a biologically effective amount of acompound of the present invention. Of further note is this methodwherein the environment is soil and the composition is applied to thesoil as a soil drench formulation. Of further note is that compounds ofthis invention are also effective by localized application to the locusof infestation. Other methods of contact include application of acompound or a composition of the invention by direct and residualsprays, aerial sprays, gels, seed coatings, microencapsulations,systemic uptake, baits, ear tags, boluses, foggers, fumigants, aerosols,dusts and many others. One embodiment of a method of contact is adimensionally stable fertilizer granule, stick or tablet comprising acompound or composition of the invention. The compounds of thisinvention can also be impregnated into materials for fabricatinginvertebrate control devices (e.g., insect netting).

Compounds of this invention are also useful in seed treatments forprotecting seeds from invertebrate pests. In the context of the presentdisclosure and claims, treating a seed means contacting the seed with abiologically effective amount of a compound of this invention, which istypically formulated as a composition of the invention. This seedtreatment protects the seed from invertebrate soil pests and generallycan also protect roots and other plant parts in contact with the soil ofthe seedling developing from the germinating seed. The seed treatmentmay also provide protection of foliage by translocation of the compoundof this invention or a second active ingredient within the developingplant. Seed treatments can be applied to all types of seeds, includingthose from which plants genetically transformed to express specializedtraits will germinate. Representative examples include those expressingproteins toxic to invertebrate pests, such as Bacillus thuringiensistoxin or those expressing herbicide resistance such as glyphosateacetyltransferase, which provides resistance to glyphosate.

One method of seed treatment is by spraying or dusting the seed with acompound of the invention (i.e. as a formulated composition) beforesowing the seeds. Compositions formulated for seed treatment generallycomprise a film former or adhesive agent. Therefore typically a seedcoating composition of the present invention comprises a biologicallyeffective amount of a compound of Formula 1 and a film former oradhesive agent. Seed can be coated by spraying a flowable suspensionconcentrate directly into a tumbling bed of seeds and then drying theseeds. Alternatively, other formulation types such as wetted powders,solutions, suspoemulsions, emulsifiable concentrates and emulsions inwater can be sprayed on the seed. This process is particularly usefulfor applying film coatings on seeds. Various coating machines andprocesses are available to one skilled in the art. Suitable processesinclude those listed in P. Kosters et al., Seed Treatment: Progress andProspects, 1994 BCPC Mongraph No. 57, and references listed therein.

The treated seed typically comprises a compound of the present inventionin an amount from about 0.1 g to 1 kg per 100 kg of seed (i.e. fromabout 0.0001 to 1% by weight of the seed before treatment). A flowablesuspension formulated for seed treatment typically comprises from about0.5 to about 70% of the active ingredient, from about 0.5 to about 30%of a film-forming adhesive, from about 0.5 to about 20% of a dispersingagent, from 0 to about 5% of a thickener, from 0 to about 5% of apigment and/or dye, from 0 to about 2% of an antifoaming agent, from 0to about 1% of a preservative, and from 0 to about 75% of a volatileliquid diluent.

The compounds of this invention can be incorporated into a baitcomposition that is consumed by an invertebrate pest or used within adevice such as a trap, bait station, and the like. Such a baitcomposition can be in the form of granules which comprise (a) activeingredients, namely a biologically effective amount of a compound ofFormula 1; (b) one or more food materials; optionally (c) an attractant,and optionally (d) one or more humectants. Of note are granules or baitcompositions which comprise between about 0.001-5% active ingredients,about 40-99% food material and/or attractant; and optionally about0.05-10% humectants, which are effective in controlling soilinvertebrate pests at very low application rates, particularly at dosesof active ingredient that are lethal by ingestion rather than by directcontact. Some food materials can function both as a food source and anattractant. Food materials include carbohydrates, proteins and lipids.Examples of food materials are vegetable flour, sugar, starches, animalfat, vegetable oil, yeast extracts and milk solids. Examples ofattractants are odorants and flavorants, such as fruit or plantextracts, perfume, or other animal or plant component, pheromones orother agents known to attract a target invertebrate pest. Examples ofhumectants, i.e. moisture retaining agents, are glycols and otherpolyols, glycerine and sorbitol. Of note is a bait composition (and amethod utilizing such a bait composition) used to control at least oneinvertebrate pest selected from the group consisting of ants, termitesand cockroaches. A device for controlling an invertebrate pest cancomprise the present bait composition and a housing adapted to receivethe bait composition, wherein the housing has at least one opening sizedto permit the invertebrate pest to pass through the opening so theinvertebrate pest can gain access to the bait composition from alocation outside the housing, and wherein the housing is further adaptedto be placed in or near a locus of potential or known activity for theinvertebrate pest.

The compounds of this invention can be applied without other adjuvants,but most often application will be of a formulation comprising one ormore active ingredients with suitable carriers, diluents, andsurfactants and possibly in combination with a food depending on thecontemplated end use. One method of application involves spraying awater dispersion or refined oil solution of a compound of the presentinvention. Combinations with spray oils, spray oil concentrations,spreader stickers, adjuvants, other solvents, and synergists such aspiperonyl butoxide often enhance compound efficacy. For nonagronomicuses such sprays can be applied from spray containers such as a can, abottle or other container, either by means of a pump or by releasing itfrom a pressurized container, e.g., a pressurized aerosol spray can.Such spray compositions can take various forms, for example, sprays,mists, foams, fumes or fog. Such spray compositions thus can furthercomprise propellants, foaming agents, etc. as needed for application. Ofnote is a spray composition comprising a biologically effective amountof a compound or a composition of the present invention and a carrier.One embodiment of such a spray composition comprises a biologicallyeffective amount of a compound or a composition of the present inventionand a propellant. Representative propellants include, but are notlimited to, methane, ethane, propane, butane, isobutane, butene,pentane, isopentane, neopentane, pentene, hydrofluorocarbons,chlorofluorocarbons, dimethyl ether, and mixtures of the foregoing. Ofnote is a spray composition (and a method utilizing such a spraycomposition dispensed from a spray container) used to control at leastone invertebrate pest selected from the group consisting of mosquitoes,black flies, stable flies, deer flies, horse flies, wasps, yellowjackets, hornets, ticks, spiders, ants, gnats, and the like, includingindividually or in combinations.

Nonagronomic uses refer to invertebrate pest control in the areas otherthan fields of crop plants. Nonagronomic uses of the present compoundsand compositions include control of invertebrate pests in stored grains,beans and other foodstuffs, and in textiles such as clothing andcarpets. Nonagronomic uses of the present compounds and compositionsalso include invertebrate pest control in ornamental plants, forests, inyards, along roadsides and railroad rights of way, and on turf such aslawns, golf courses and pastures. Nonagronomic uses of the presentcompounds and compositions also include invertebrate pest control inhouses and other buildings which may be occupied by humans and/orcompanion, farm, ranch, zoo or other animals. Nonagronomic uses of thepresent compounds and compositions also include the control of pestssuch as termites that can damage wood or other structural materials usedin buildings.

Nonagronomic uses of the present compounds and compositions also includeprotecting human and animal health by controlling invertebrate peststhat are parasitic or transmit infectious diseases. The controlling ofanimal parasites includes controlling external parasites that areparasitic to the surface of the body of the host animal (e.g.,shoulders, armpits, abdomen, inner part of the thighs) and internalparasites that are parasitic to the inside of the body of the hostanimal (e.g., stomach, intestine, lung, veins, under the skin, lymphatictissue). External parasitic or disease transmitting pests include, forexample, chiggers, ticks, lice, mosquitoes, flies, mites and fleas.Internal parasites include heartworms, hookworms and helminths.Compounds and compositions of the present invention are particularlysuitable for combating external parasitic or disease transmitting pests.Compounds and compositions of the present invention are suitable forsystemic and/or non-systemic control of infestation or infection byparasites on animals.

Compounds and compositions of the present invention are suitable forcombating parasites that infest animal subjects including those in thewild, livestock and agricultural working animals such as cattle, sheep,goats, horses, pigs, donkeys, camels, bison, buffaloes, rabbits, hens,turkeys, ducks, geese and bees (e.g., raised for meat, milk, butter,eggs, fur, leather, feathers and/or wool). By combating parasites,fatalities and performance reduction (in terms of meat, milk, wool,skins, eggs, honey, etc.) are reduced, so that applying a compositioncomprising a compound of the present invention allows more economic andsimple husbandry of animals.

Compounds and compositions of the present invention are especiallysuitable for combating parasites that infest companion animals and pets(e.g., dogs, cats, pet birds and aquarium fish), research andexperimental animals (e.g., hamsters, guinea pigs, rats and mice), aswell as animals raised for/in zoos, wild habitats and/or circuses.

In an embodiment of this invention, the animal is preferably avertebrate, and more preferably a mammal, avian or fish. In a particularembodiment, the animal subject is a mammal (including great apes, suchas humans). Other mammalian subjects include primates (e.g., monkeys),bovine (e.g., cattle or dairy cows), porcine (e.g., hogs or pigs), ovine(e.g., goats or sheep), equine (e.g., horses), canine (e.g., dogs),feline (e.g., house cats), camels, deer, donkeys, bison, buffaloes,antelopes, rabbits, and rodents (e.g., guinea pigs, squirrels, rats,mice, gerbils, and hamsters). Avians include Anatidae (swans, ducks andgeese), Columbidae (e.g., doves and pigeons), Phasianidae (e.g.,partridges, grouse and turkeys), Thesienidae (e.g., domestic chickens),Psittacines (e.g., parakeets, macaws, and parrots), game birds, andratites (e.g., ostriches).

Birds treated or protected by the inventive compounds can be associatedwith either commercial or noncommercial aviculture. These includeAnatidae, such as swans, geese, and ducks, Columbidae, such as doves anddomestic pigeons, Phasianidae, such as partridge, grouse and turkeys,Thesienidae, such as domestic chickens, and Psittacines, such asparakeets, macaws, and parrots raised for the pet or collector market,among others.

For purposes of the present invention, the term “fish” shall beunderstood to include without limitation, the Teleosti grouping of fish,i.e., teleosts. Both the Salmoniformes order (which includes theSalmonidae family) and the Perciformes order (which includes theCentrarchidae family) are contained within the Teleosti grouping.Examples of potential fish recipients include the Salmonidae,Serranidae, Sparidae, Cichlidae, and Centrarchidae, among others.

Other animals are also contemplated to benefit from the inventivemethods, including marsupials (such as kangaroos), reptiles (such asfarmed turtles), and other economically important domestic animals forwhich the inventive methods are safe and effective in treating orpreventing parasite infection or infestation.

Examples of invertebrate parasitic pests controlled by administering aparasiticidally effective amount of a compound of this invention to ananimal to be protected include ectoparasites (arthropods, acarines, etc)and endoparasites (helminths, e.g., nematodes, trematodes, cestodes,acanthocephalans, etc.).

The disease or group of diseases described generally as helminthiasis isdue to infection of an animal host with parasitic worms known ashelminths. The term ‘helminths’ is meant to include nematodes,trematodes, cestodes and acanthocephalans. Helminthiasis is a prevalentand serious economic problem with domesticated animals such as swine,sheep, horses, cattle, goats, dogs, cats and poultry.

Among the Helminths, the group of worms described as nematodes causeswidespread and at times serious infection in various species of animals.Nematodes that are contemplated to be treated by the compounds of thisinvention and by the inventive methods include, without limitation, thefollowing genera: Acanthocheilonema, Aelurostrongylus, Ancylostoma,Angiostrongylus, Ascaridia, Ascaris, Brugia, Bunostomum, Capillaria,Chabertia, Cooperia, Crenosoma, Dictyocaulus, Dioctophyme, Dipetalonema,Diphyllobothrium, Dirofilaria, Dracunculus, Enterobius, Filaroides,Haemonchus, Heterakis, Lagochilascaris, Loa, Mansonella, Muellerius,Necator, Nematodirus, Oesophagostomum, Ostertagia, Oxyuris, Parafilaria,Parascaris, Physaloptera, Protostrongylus, Setaria, Spirocerca,Stephanofilaria, Strongyloides, Strongylus, Thelazia, Toxascaris,Toxocara, Trichinella, Trichonema, Trichostrongylus, Trichuris,Uncinaria, and Wuchereria.

Of the above, the most common genera of nematodes infecting the animalsreferred to above are Haemonchus, Trichostrongylus, Ostertagia,Nematodirus, Cooperia, Ascaris, Bunostomum, Oesophagostomum, Chabertia,Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis,Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris andParascaris. Certain of these, such as Nematodirus, Cooperia andOesophagostomum attack primarily the intestinal tract while others, suchas Haemonchus and Ostertagia, are more prevalent in the stomach whileothers such as Dictyocaulus are found in the lungs. Still otherparasites may be located in other tissues such as the heart and bloodvessels, subcutaneous and lymphatic tissue and the like.

Trematodes that are contemplated to be treated by the compounds of thisinvention and by the inventive methods include, without limitation, thefollowing genera: Alaria, Fasciola, Nanophyetus, Opisthorchis,Paragonimus and Schistosoma.

Cestodes that are contemplated to be treated by the compounds of thisinvention and by the inventive methods include, without limitation, thefollowing genera: Diphyllobothrium, Diplydium, Spirometra and Taenia.

The most common genera of parasites of the gastrointestinal tract ofhumans are Ancylostoma, Necator, Ascaris, Strongyloides, Trichinella,Capillaria, Trichuris, and Enterobius. Other medically important generaof parasites which are found in the blood or other tissues and organsoutside the gastrointestinal tract are the filarial worms such asWuchereria, Brugia, Onchocerca and Loa, as well as Dracunculus and extraintestinal stages of the intestinal worms Strongyloides and Trichinella.

Numerous other Helminth genera and species are known to the art, and arealso contemplated to be treated by the compounds of the invention. Theseare enumerated in great detail in Textbook of Veterinary ClinicalParasitology, Volume 1, Helminths, E. J. L. Soulsby, F. A. Davis Co.,Philadelphia, Pa.; Helminths, Arthropods and Protozoa, (6^(th) Editionof Monnig's Veterinary Helminthology and Entomology), E. J. L. Soulsby,The Williams and Wilkins Co., Baltimore, Md.

It is also contemplated that the inventive compounds are effectiveagainst a number of ectoparasites of animals, e.g., arthropodectoparasites of mammals and birds although it is also recognized thatsome arthropods can be endoparasites as well.

Thus, insect and acarine pests include, e.g., biting insects, such asflies and mosquitoes, mites, ticks, lice, fleas, true bugs, parasiticmaggots, and the like.

Adult flies include, e.g., the horn fly or Haematobia irritans, thehorse fly or Tabanus spp., the stable fly or Stomoxys calcitrans, theblack fly or Simulium spp., the deer fly or Chrysops spp., the louse flyor Melophagus ovinus, the tsetse fly or Glossina spp. Parasitic flymaggots include, e.g., the bot fly (Oestrus ovis and Cuterebra spp.),the blow fly or Phaenicia spp., the screwworm or Cochliomyiahominivorax, the cattle grub or Hypoderma spp., the fleeceworm and theGastrophilus of horses. Mosquitoes include, for example, Culex spp.,Anopheles spp., and Aedes spp.

Mites include Mesostigmata spp. e.g., mesostigmatids such as the chickenmite, Dermanyssus gallinae; itch or scab mites such as Sarcoptidae spp.for example, Sarcoptes scabiei; mange mites such as Psoroptidae spp.including Chorioptes bovis and Psoroptes ovis; chiggers e.g.,Trombiculidae spp. for example the North American chigger, Trombiculaalfreddugesi.

Ticks include, e.g., soft-bodied ticks including Argasidae spp. forexample Argas spp. and Ornithodoros spp.; hard-bodied ticks includingIxodidae spp., for example Rhipicephalus sanguineus, Dermacentorvariabilis, Dermacentor andersoni, Amblyomma americanum, Ixodesscapularis and Boophilus spp.

Lice include, e.g., sucking lice, e.g., Menopon spp. and Bovicola spp.;biting lice, e.g., Haematopinus spp., Linognathus spp. and Solenopotesspp.

Fleas include, e.g., Ctenocephalides spp., such as dog flea(Ctenocephalides canis) and cat flea (Ctenocephalides felis); Xenopsyllaspp. such as oriental rat flea (Xenopsylla cheopis); and Pulex spp. suchas human flea (Pulex irritans).

True bugs include, e.g., Cimicidae or e.g., the common bed bug (Cimexlectularius); Triatominae spp. including triatomid bugs also known askissing bugs; for example Rhodnius prolixus and Triatoma spp.

Generally, flies, fleas, lice, mosquitoes, gnats, mites, ticks andhelminths cause tremendous losses to the livestock and companion animalsectors. Arthropod parasites also are a nuisance to humans and canvector disease-causing organisms in humans and animals.

Numerous other arthropod pests and ectoparasites are known to the art,and are also contemplated to be treated by the compounds of theinvention. These are enumerated in great detail in Medical andVeterinary Entomology, D. S. Kettle, John Wiley & Sons, New York andToronto; Control of Arthropod Pests of Livestock: A Review ofTechnology, R. O. Drummand, J. E. George, and S. E. Kunz, CRC Press,Boca Raton, Fla.

The compounds and compositions of this invention may also be effectiveagainst a number of protozoa endoparasites of animals, such as thosesummarized by Table 1, as follows.

TABLE 1 Exemplary Parasitic Protozoa and Associated Human DiseasesRepresentative Human Disease Phylum Subphylum Genera or DisorderSarcomastigophora Mastigophora Leishmania Visceral, (with flagella,(Flagella) cutaneous and pseudopodia, or mucocutaneous both) InfectionTrypansoma Sleeping sickness Chagas' disease Giardia DiarrheaTrichomonas Vaginitis Sarcodina Entamoeba Dysentery, (pseudopodia) liverAbscess Dientamoeba Colitis Naegleria and Central Acanthamoeba nervoussystem and corneal ulcers Babesia Babesiesis Apicomplexa PlasmodiumMalaria (apical complex) Isospora Diarrhea Sarcocystis DiarrheaCryptosporidum Diarrhea Toxoplasma Toxoplasmosis Eimeria Chickencoccidiosis Microspora Enterocytozoon Diarrhea Ciliaphora (withBalantidium Dysentery cilia) Unclassified Pneumocystis Pneumonia

In particular, the compounds of this invention are effective againstectoparasites including fleas such as Ctenocephalides felis (cat flea)and Ctenocephalides canis (dog flea).

The compounds of this invention may also be effective against otherectoparasites including flies such as Haematobia (Lyperosia) irritans(horn fly), Stomoxys calcitrans (stable fly), Simulium spp. (blackfly),Glossina spp. (tsetse flies), Hydrotaea irritans (head fly), Muscaautumnalis (face fly), Musca domestica (house fly), Morellia simplex(sweat fly), Tabanus spp. (horse fly), Hypoderma bovis, Hypodermalineatum, Lucilia sericata, Lucilia cuprina (green blowfly), Calliphoraspp. (blowfly), Protophormia spp., Oestrus ovis (nasal botfly),Culicoides spp. (midges), Hippobosca equine, Gastrophilus instestinalis,Gastrophilus haemorrhoidalis and Gastrophilus naslis; lice such asBovicola (Damalinia) bovis, Bovicola equi, Haematopinus asini, Felicolasubrostratus, Heterodoxus spiniger, Lignonathus setosus and Trichodectescanis; keds such as Melophagus ovinus; mites such as Psoroptes spp.,Sarcoptes scabei, Chorioptes bovis, Demodex equi, Cheyletiella spp.,Notoedres cati, Trombicula spp. and Otodectes cyanotis (ear mites); andticks such as Ixodes spp., Boophilus spp., Rhipicephalus spp., Amblyommaspp., Dermacentor spp., Hyalomma spp. and Haemaphysalis spp.

Biologically active compounds or agents useful in the compositions ofthe present invention include the organophosphate pesticides. This classof pesticides has very broad activity as insecticides and, in certaininstances, anthelminitic activity. Organophosphate pesticides include,e.g., dicrotophos, terbufos, dimethoate, diazinon, disulfoton,trichlorfon, azinphos-methyl, chlorpyrifos, malathion,oxydemeton-methyl, methamidophos, acephate, ethyl parathion, methylparathion, mevinphos, phorate, carbofenthion and phosalone. It is alsocontemplated to include combinations of the inventive methods andcompounds with carbamate type pesticides, including, e.g., carbaryl,carbofuran, aldicarb, molinate, methomyl, carbofuran, etc., as well ascombinations with the organochlorine type pesticides. It is furthercontemplated to include combinations with biological pesticides,including repellents, the pyrethrins (as well as synthetic variationsthereof, e.g., allethrin, resmethrin, permethrin, tralomethrin), andnicotine, that is often employed as an acaricide. Other contemplatedcombinations are with miscellaneous pesticides including: bacillusthuringensis, chlorobenzilate, formamidines (e.g., amitraz), coppercompounds (e.g., copper hydroxide and cupric oxychloride sulfate),cyfluthrin, cypermethrin, dicofol, endosulfan, esenfenvalerate,fenvalerate, lambda-cyhalothrin, methoxychlor and sulfur.

Of note are additional biologically active compounds or agents selectedfrom art-known anthelmintics, such as, for example, avermectins (e.g.,ivermectin, moxidectin, milbemycin), benzimidazoles (e.g., albendazole,triclabendazole), salicylanilides (e.g., closantel, oxyclozanide),substituted phenols (e.g., nitroxynil), pyrimidines (e.g., pyrantel),imidazothiazoles (e.g., levamisole) and praziquantel.

Other biologically active compounds or agents useful in the compositionsof the present invention can be selected from Insect Growth Regulators(IGRs) and Juvenile Hormone Analogues (JHAs) such as diflubenzuron,triflumuron, fluazuron, cyromazine, methoprene, etc., thereby providingboth initial and sustained control of parasites (at all stages of insectdevelopment, including eggs) on the animal subject, as well as withinthe environment of the animal subject.

Of note are biologically active compounds or agents useful in thecompositions of the present invention selected from the antiparasiticclass of avermectin compounds. As stated above, the avermectin family ofcompounds is a series of very potent antiparasitic agents known to beuseful against a broad spectrum of endoparasites and ectoparasites inmammals.

A notable compound for use within the scope of the present invention isivermectin. Ivermectin is a semi-synthetic derivative of avermectin andis generally produced as a mixture of at least 80%22,23-dihydroavermectin B_(1a) and less than 20% 22,23-dihydroavermectinB_(1b). Ivermectin is disclosed in U.S. Pat. No. 4,199,569.

Abamectin is an avermectin that is disclosed as Avermectin B_(1a)/B_(1b)in U.S. Pat. No. 4,310,519. Abamectin contains at least 80% ofavermectin B_(1a) and not more than 20% of avermectin B_(1b).

Another notable avermectin is Doramectin, also known as25-cyclohexyl-avermectin B₁. The structure and preparation of Doramectinis disclosed in U.S. Pat. No. 5,089,480.

Another notable avermectin is Moxidectin. Moxidectin, also known asLL-F28249 alpha, is known from U.S. Pat. No. 4,916,154.

Another notable avermectin is Selamectin. Selamectin is25-cyclohexyl-25-de(1-methylpropyl)-5-deoxy-22,23-dihydro-5-(hydroxyimino)-avermectinB₁ monosaccharide.

Milbemycin, or B41, is a substance which is isolated from thefermentation broth of a Milbemycin producing strain of Streptomyces. Themicroorganism, the fermentation conditions and the isolation proceduresare more fully described in U.S. Pat. No. 3,950,360 and U.S. Pat. No.3,984,564.

Emamectin (4″-deoxy-4″-epi-methylaminoavermectin B₁), which can beprepared as described in U.S. Pat. No. 5,288,710 or U.S. Pat. No.5,399,717, is a mixture of two homologues,4″-deoxy-4″-epi-methylaminoavermectin B_(1a) and4″-deoxy-4″-epi-methylaminoavermectin B_(1b). Preferably, a salt ofEmamectin is used. Non-limiting examples of salts of Emamectin which canbe used in the present invention include the salts described in U.S.Pat. No. 5,288,710, e.g., salts derived from benzoic acid, substitutedbenzoic acid, benzenesulfonic acid, citric acid, phosphoric acid,tartaric acid, maleic acid, and the like. Most preferably, the Emamectinsalt used in the present invention is Emamectin benzoate.

Eprinomectin is chemically known as4″-epi-acetylamino-4″-deoxy-avermectin B₁. Eprinomectin was specificallydeveloped to be used in all cattle classes and age groups. It was thefirst avermectin to show broad-spectrum activity against both endo- andecto-parasites while also leaving minimal residues in meat and milk. Ithas the additional advantage of being highly potent when deliveredtopically.

The composition of the present invention optionally comprisescombinations of one or more of the following antiparasite compounds:imidazo[1,2-b]pyridazine compounds as described by U.S. application Ser.No. 11/019,597, filed on Dec. 22, 2004; 1-(4-mono anddi-halomethylsulphonylphenyl)-2-acylamino-3-fluoropropanol compounds, asdescribed by U.S. application Ser. No. 11/018,156, filed on Dec. 21,2004; trifluoromethanesulfonanilide oxime ether derivatives, asdescribed by U.S. application Ser. No. 11/231,423, filed on Sep. 21,2005; and n-[(phenyloxy)phenyl]-1,1,1-trifluoromethanesulfonamide andn-[(phenylsulfanyl)phenyl]-1,1,1-trifluoromethanesulfonamidederivatives, as described by U.S. Provisional Application Ser. No.60/688,898, filed on Jun. 9, 2005.

The compositions of the present invention can also further comprise aflukicide. Suitable flukicides include, for example, triclabendazole,fenbendazole, albendazole, Clorsulon and oxibendazole. It will beappreciated that the above combinations can further include combinationsof antibiotic, antiparasitic and anti-fluke active compounds.

In addition to the above combinations, it is also contemplated toprovide combinations of the inventive methods and compounds, asdescribed herein, with other animal health remedies such as traceelements, anti-inflammatories, anti-infectives, hormones, dermatologicalpreparations, including antiseptics and disinfectants, andimmunobiologicals such as vaccines and antisera for the prevention ofdisease.

For example, such antinfectives include one or more antibiotics that areoptionally co-administered during treatment using the inventivecompounds or methods, e.g., in a combined composition and/or in separatedosage forms. Art-known antibiotics suitable for this purpose include,for example, those listed herein below.

One useful antibiotic is Florfenicol, also known asD-(threo)-1-(4-methylsulfonylphenyl)-2-dichloroacetamido-3-fluoro-1-propanol.Another notable antibiotic compound isD-(threo)-1-(4-methylsulfonylphenyl)-2-difluoroacetamido-3-fluoro-1-propanol.Another useful antibiotic is Thiamphenicol. Processes for themanufacture of these antibiotic compounds, and intermediates useful insuch processes, are described in U.S. Pat. No. 4,311,857; U.S. Pat. No.4,582,918; U.S. Pat. No. 4,973,750; U.S. Pat. No. 4,876,352; U.S. Pat.No. 5,227,494; U.S. Pat. No. 4,743,700; U.S. Pat. No. 5,567,844; U.S.Pat. No. 5,105,009; U.S. Pat. No. 5,382,673; U.S. Pat. No. 5,352,832;and U.S. Pat. No. 5,663,361. Other florfenicol analogs and/or prodrugshave been disclosed and such analogs also can be used in thecompositions and methods of the present invention (see e.g., U.S. PatentApplication Publication No: 2004/0082553, and U.S. patent applicationSer. No. 11/016,794).

Another useful antibiotic compound is Tilmicosin. Tilmicosin is amacrolide antibiotic that is chemically defined as20-dihydro-20-deoxy-20-(cis-3,5-dimethylpiperidin-1-yl)-desmycosin andwhich is reportedly disclosed in U.S. Pat. No. 4,820,695.

Another useful antibiotic for use in the present invention istulathromycin. Tulathromycin is also identified as(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-4-C-[(propylamino)methyl]-alpha-L-ribo-hexopyranosyl]-oxy]-2-ethyl-3,4,10-trihydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethyl-amino)-beta-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one.Tulathromycin can be prepared in accordance with the procedures setforth in U.S. Patent Publication No. 2003/0064939 A1.

Further antibiotics for use in the present invention include thecephalosporins such as, for example, ceftiofur, cefquinome, etc. Theconcentration of the cephalosporin in the formulation of the presentinvention optionally varies between about 1 mg/mL to 500 mg/mL.

Another useful antibiotic includes the fluoroquinolones, such as, forexample, enrofloxacin, danofloxacin, difloxacin, orbifloxacin andmarbofloxacin. Enrofloxacin is typically administered in a concentrationof about 100 mg/mL. Danofloxacin is typically administered at aconcentration of about 180 mg/mL.

Other useful macrolide antibiotics include compounds from the class ofketolides, or, more specifically, the azalides. Such compounds aredescribed in, for example, U.S. Pat. No. 6,514,945, U.S. Pat. No.6,472,371, U.S. Pat. No. 6,270,768, U.S. Pat. No. 6,437,151, U.S. Pat.No. 6,271,255, U.S. Pat. No. 6,239,112, U.S. Pat. No. 5,958,888, U.S.Pat. No. 6,339,063 and U.S. Pat. No. 6,054,434.

Other useful antibiotics include the tetracyclines, particularlychlortetracycline and oxytetracycline. Other antibiotics may includeβ-lactams such as penicillins, e.g., penicillin, ampicillin,amoxicillin, or a combination of amoxicillin with clavulanic acid orother beta lactamase inhibitors.

Nonagronomic applications in the veterinary sector are by conventionalmeans such as by enteral administration in the form of, for example,tablets, capsules, drinks, drenching preparations, granulates, pastes,boli, feed-through procedures, or suppositories; or by parenteraladministration, such as by injection (including intramuscular,subcutaneous, intravenous, intraperitoneal) or implants; by nasaladministration; by topical administration, for example, in the form ofimmersion or dipping, spraying, washing, coating with powder, orapplication to a small area of the animal, and through articles such asneck collars, ear tags, tail bands, limb bands or halters which comprisecompounds or compositions of the present invention.

Any of the compounds of the present invention, or a suitable combinationof such compounds, may be administered directly to the animal subjectand/or indirectly by applying it to the local environment in which theanimal dwells (such as bedding, enclosures, or the like). Directadministration includes contacting the skin, fur or feathers of asubject animal with the compounds, or by feeding or injecting thecompounds into the animal.

The compounds of the present invention may be administered in acontrolled release form, e.g., in a subcutaneous slow releaseformulation, or in the form of a controlled release device affixed to ananimal such as a fleacollar. Collars for the controlled release of aninsecticide agent for long term protection against flea infestation in acompanion animal are art-known, and are described, for example, by U.S.Pat. No. 3,852,416, U.S. Pat. No. 4,224,901, U.S. Pat. No. 5,555,848 andU.S. Pat. No. 5,184,573.

Typically a parasiticidal composition according to the present inventioncomprises a mixture of a compound of Formula 1 with one or morepharmaceutically or veterinarily acceptable carriers comprisingexcipients and auxiliaries selected with regard to the intended route ofadministration (e.g., oral, topical or parenteral administration such asinjection) and in accordance with standard practice. In addition, asuitable carrier is selected on the basis of compatibility with the oneor more active ingredients in the composition, including suchconsiderations as stability relative to pH and moisture content.Therefore of note is a composition for protecting an animal from aninvertebrate parasitic pest comprising a parasitically effective amountof a compound of the invention and at least one carrier.

For parenteral administration including intravenous, intramuscular andsubcutaneous injection, a compound of the present invention can beformulated in suspension, solution or emulsion in oily or aqueousvehicles, and may contain adjuncts such as suspending, stabilizingand/or dispersing agents. The compounds of the present invention mayalso be formulated for bolus injection or continuous infusion.Pharmaceutical compositions for injection include aqueous solutions ofwater-soluble forms of active ingredients (e.g., a salt of an activecompound), preferably in physiologically compatible buffers containingother excipients or auxiliaries as are known in the art ofpharmaceutical formulation. Additionally, suspensions of the activecompounds may be prepared in a lipophilic vehicle. Suitable lipophilicvehicles include fatty oils such as sesame oil, synthetic fatty acidesters such as ethyl oleate and triglycerides, or materials such asliposomes. Aqueous injection suspensions may contain substances thatincrease the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol, or dextran. Formulations for injection may bepresented in unit dosage form, e.g., in ampoules or in multi-dosecontainers. Alternatively, the active ingredient may be in powder formfor constitution with a suitable vehicle, e.g., sterile, pyrogen-freewater, before use.

In addition to the formulations described supra, the compounds of thepresent invention may also be formulated as a depot preparation. Suchlong acting formulations may be administered by implantation (forexample, subcutaneously or intramuscularly) or by intramuscular orsubcutaneous injection. The compounds of the present invention may beformulated for this route of administration with suitable polymeric orhydrophobic materials (for instance, in an emulsion with apharmacologically acceptable oil), with ion exchange resins, or as asparingly soluble derivative such as, without limitation, a sparinglysoluble salt.

For administration by inhalation, the compounds of the present inventioncan be delivered in the form of an aerosol spray using a pressurizedpack or a nebulizer and a suitable propellant, e.g., without limitation,dichlorodifluoromethane, trichlorofluoromethane,dichlorotetrafluoroethane or carbon dioxide. In the case of apressurized aerosol, the dosage unit may be controlled by providing avalve to deliver a metered amount. Capsules and cartridges of, forexample, gelatin for use in an inhaler or insufflator may be formulatedcontaining a powder mix of the compound and a suitable powder base suchas lactose or starch.

Compounds of the present invention have been discovered to havefavorable pharmacokinetic and pharmacodynamic properties providingsystemic availability from oral administration and ingestion. Thereforeafter ingestion by the animal to be protected, parasiticidally effectiveconcentrations of compounds of the invention in the bloodstream protectthe treated animal from blood-sucking pests such as fleas, ticks andlice. Therefore of note is a composition for protecting an animal froman invertebrate parasite pest in a form for oral administration (i.e.comprising, in addition to a parasiticidally effective amount of acompound of the invention, one or more carriers selected from bindersand fillers suitable for oral administration and feed concentratecarriers).

For oral administration in the form of solutions (the most readilyavailable form for absorption), emulsions, suspensions, pastes, gels,capsules, tablets, boluses, powders, granules, rumen-retention andfeed/water/lick blocks, a compound of the present invention can beformulated with binders/fillers known in the art to be suitable for oraladministration compositions, such as sugars and sugar derivatives (e.g.,lactose, sucrose, mannitol, sorbitol), starch (e.g., maize starch, wheatstarch, rice starch, potato starch), cellulose and derivatives (e.g.,methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), proteinderivatives (e.g., zein, gelatin), and synthetic polymers (e.g.,polyvinyl alcohol, polyvinylpyrrolidone). If desired, lubricants (e.g.,magnesium stearate), disintegrating agents (e.g., cross-linkedpolyvinylpyrrolidinone, agar, alginic acid) and dyes or pigments can beadded. Pastes and gels often also contain adhesives (e.g., acacia,alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesiumaluminum silicate) to aid in keeping the composition in contact with theoral cavity and not being easily ejected.

If the parasiticidal compositions are in the form of feed concentrates,the carrier is typically selected from high-performance feed, feedcereals or protein concentrates. Such feed concentrate-containingcompositions can, in addition to the parasiticidal active ingredients,comprise additives promoting animal health or growth, improving qualityof meat from animals for slaughter or otherwise useful to animalhusbandry. These additives can include, for example, vitamins,antibiotics, chemotherapeutics, bacteriostats, fungistats, coccidiostatsand hormones.

The compounds of Formula 1 may also be formulated in rectal compositionssuch as suppositories or retention enemas, using, e.g., conventionalsuppository bases such as cocoa butter or other glycerides.

Formulations for topical administration are typically in the form of apowder, cream, suspension, spray, emulsion, foam, paste, aerosol,ointment, salve or gel. More typically a topical formulation is awater-soluble solution, which can be in the form of a concentrate thatis diluted before use. Parasiticidal compositions suitable for topicaladministration typically comprise a compound of the present inventionand one or more topically suitable carriers. In applications of aparasiticidal composition topically to the exterior of an animal as aline or spot (i.e. “spot-on” treatment), the active ingredient migratesover the surface of the animal to cover most or all of its externalsurface area. As a result, the treated animal is particularly protectedfrom invertebrate pests that feed off the epidermis of the animal suchas ticks, fleas and lice. Therefore formulations for topical localizedadministration often comprise at least one organic solvent to facilitatetransport of the active ingredient over the skin and/or penetration intothe epidermis of the animal. Carriers in such formulations includepropylene glycol, paraffins, aromatics, esters such as isopropylmyristate, glycol ethers, alcohols such as ethanol, n-propanol, 2-octyldodecanol or oleyl alcohol; solutions in esters of monocarboxylic acids,such as isopropyl myristate, isopropyl palmitate, lauric acid oxalicester, oleic acid oleyl ester, oleic acid decyl ester, hexyl laurate,oleyl oleate, decyl oleate, caproic acid esters of saturated fattyalcohols of chain length C₁₂-C₁₈; solutions of esters of dicarboxylicacids, such as dibutyl phthalate, diisopropyl isophthalate, adipic aciddiisopropyl ester, di-n-butyl adipate or solutions of esters ofaliphatic acids, e.g., glycols. It may be advantageous for acrystallization inhibitor or a dispersant known from the pharmaceuticalor cosmetic industry also to be present.

A pour-on formulation may also be prepared for control of parasites inan animal of agricultural worth. The pour-on formulations of thisinvention can be in the form of a liquid, powder, emulsion, foam, paste,aerosol, ointment, salve or gel. Typically, the pour-on formulation isliquid. These pour-on formulations can be effectively applied to sheep,cattle, goats, other ruminants, camelids, pigs and horses. The pour-onformulation is typically applied by pouring in one or several lines orin a spot-on the dorsal midline (back) or shoulder of an animal. Moretypically, the formulation is applied by pouring it along the back ofthe animal, following the spine. The formulation can also be applied tothe animal by other conventional methods, including wiping animpregnated material over at least a small area of the animal, orapplying it using a commercially available applicator, by means of asyringe, by spraying or by using a spray race. The pour-on formulationsinclude a carrier and can also include one or more additionalingredients. Examples of suitable additional ingredients are stabilizerssuch as antioxidants, spreading agents, preservatives, adhesionpromoters, active solubilisers such as oleic acid, viscosity modifiers,UV blockers or absorbers, and colourants. Surface active agents,including anionic, cationic, non-ionic and ampholytic surface activeagents, can also be included in these formulations.

The formulations of this invention typically include an antioxidant,such as BHT (butylated hydroxytoluene). The antioxidant is generallypresent in amounts of at 0.1-5% (wt/vol). Some of the formulationsrequire a solubilizer, such as oleic acid, to dissolve the active agent,particularly if spinosad is used. Common spreading agents used in thesepour-on formulations are: IPM, IPP, caprylic/capric acid esters ofsaturated C₁₂-C₁₈ fatty alcohols, oleic acid, oleyl ester, ethyl oleate,triglycerides, silicone oils and DPM. The pour-on formulations of thisinvention are prepared according to known techniques. Where the pour-onis a solution, the parasiticide/insecticide is mixed with the carrier orvehicle, using heat and stirring where required. Auxiliary or additionalingredients can be added to the mixture of active agent and carrier, orthey can be mixed with the active agent prior to the addition of thecarrier. If the pour-on is an emulsion or suspension, these formulationsare similarly prepared using known techniques.

Other delivery systems for relatively hydrophobic pharmaceuticalcompounds may be employed. Liposomes and emulsions are well-knownexamples of delivery vehicles or carriers for hydrophobic drugs. Inaddition, organic solvents such as dimethylsulfoxide may be used, ifneeded.

For agronomic applications, the rate of application required foreffective control (i.e. “biologically effective amount”) will depend onsuch factors as the species of invertebrate to be controlled, the pest'slife cycle, life stage, its size, location, time of year, host crop oranimal, feeding behavior, mating behavior, ambient moisture,temperature, and the like. Under normal circumstances, application ratesof about 0.01 to 2 kg of active ingredients per hectare are sufficientto control pests in agronomic ecosystems, but as little as 0.0001kg/hectare may be sufficient or as much as 8 kg/hectare may be required.For nonagronomic applications, effective use rates will range from about1.0 to 50 mg/square meter but as little as 0.1 mg/square meter may besufficient or as much as 150 mg/square meter may be required. Oneskilled in the art can easily determine the biologically effectiveamount necessary for the desired level of invertebrate pest control.

In general for veterinary use, a compound of Formula 1 is administeredin a parasiticidally effective amount to an animal to be protected frominvertebrate parasite pests. A parasiticidally effective amount is theamount of active ingredient needed to achieve an observable effectdiminishing the occurrence or activity of the target invertebrateparasite pest. One skilled in the art will appreciate that theparasitically effective dose can vary for the various compounds andcompositions of the present invention, the desired parasitical effectand duration, the target invertebrate pest species, the animal to beprotected, the mode of application and the like, and the amount neededto achieve a particular result can be determined through simpleexperimentation.

For oral administration to homeothermic animals, the daily dosage of acompound of the present invention typically ranges from about 0.01 mg/kgto about 100 mg/kg, more typically from about 0.5 mg/kg to about 100mg/kg, of animal body weight. For topical (e.g., dermal) administration,dips and sprays typically contain from about 0.5 ppm to about 5000 ppm,more typically from about 1 ppm to about 3000 ppm, of a compound of thepresent invention.

The compounds of this invention prepared by the methods described hereinare shown in Index Tables A-F. See Index Table G for ¹H NMR data. Formass spectral data (AP⁺ (M+1)), the numerical value reported is themolecular weight of the parent molecular ion (M) formed by addition ofH⁺ (molecular weight of 1) to the molecule to give a M+1 peak observedby mass spectrometry using atmospheric pressure chemical ionization(AP⁺). The alternate molecular ion peaks (e.g., M+2 or M+4) that occurwith compounds containing multiple halogens are not reported. Thevariable “R^(a)” in Index Table C represents one or a combination ofsubstituents as listed in Index Table C.

The following additional abbreviations are used in the Index Tableswhich follow: Cmpd means Compound, Me is methyl, Et is ethyl, i-Pr isisopropyl, n-Bu is normal-butyl, t-Bu is tertiary-butyl, Ph is phenyl,CHO is formyl, Ac is acetyl (i.e. C(O)CH₃) and SO₂Me is methyl sulfonyl.

Fragments A-1 through A-42 and B-1 through B-4 shown below are referredto in the Index Tables. The asterisk * denotes the attachment point ofthe fragment to the remainder of the molecule.

INDEX TABLE A

AP+ Cmpd R² R^(a) R^(b) R^(c) R^(d) R^(e) m.p. (° C.) (M + 1)  1 CH₂CF₃H Br H H H 233-234  2 CH₂CF₃ H OCH₃ H H H 124-125  3 CH₂CF₃ H Cl H H H * 5 CH₂CF₃ H H F H H 205-206  6 CH₂CF₃ H CF₃ H H H 178-179  7 CH₂CF₃ H HH H H **  8 CH₂CH₂CH₃ H OCF₃ H H H *  9 CH₂CF₃ Cl Cl H H H *  10 CH₂CF₃F H F H H *  11 CH₂CF₃ F H H H H 211-212  12 CH₂CH₂CH₃ H CF₃ H H H *  13CH₂CF₃ H OCH₂CF₃ H H H 162-163  14 CH₂CF₃ F H H OCF₃ H *  15 CH₂CF₃ H ClH Cl H *  16 CH₂CF₃ H CH₃ F H H 239-240  17 CH₂CF₃ OCH₃ H H H H *  18A-3 H OCF₃ H H H *  19 A-3 H H F H H 188-189  20 CH₂CH₂CH₃ H F H F H * 21 CH₂CF₃ F H Cl H H *  22 A-8 H OCF₃ H H H *  23 CH₂CF₃ H F F H H118-119  24 CH₂CF₃ H Br F H H 213-214  25 CH₂CF₃ OCH₃ H H Cl H *  26CH₂CF₃ H H Cl H H 226-227  27 A-8 H H F H H *  28 CH₂CH₂CH₃ H H H H H * 29 A-3 Cl H F H H 191-192  30 A-8 F H F H H *  31 A-3 F H F H H 204-205 32 CH₂CF₃ H F H F H *  33 CH₂CF₂CF₃ H OCF₃ H H H *  34 CH₂CF₂CF₃ H H HH H *  35 CH₂CF₂CF₃ H H F H H *  36 CH₂CF₂CF₃ F H F H H *  37 CH₂CF═CF₂H H H H H *  38 CH₂CH₂CF₃ H H H H H *  39 A-3 H H H H H *  40 CH₂CF₃ HOCF₃ H H H 140-141  41 CH₂CH₂CH₃ H H cyano H H * 122 CH₂CH═CH₂ H H H H H**  42 A-1 H H F H H *  43 A-1 H H H H H 233-235  44 A-1 F H F H H *  45A-1 H OCF₃ H H H 123-125  46 A-1 H CF₃ H H H 152-153  47 A-1 H Cl H H H235-237  48 A-1 H H OCHF₂ H H 182-183  49 A-1 H H OCH₃ H H 215-217  50A-1 F H H H H *  51 A-2 H Br H H H *  52 A-2 H Cl H CF₃ H *  53 A-2 HCF₃ H H H *  54 A-2 H OCF₃ H H H *  55 A-2 H Br H OCF₃ H *  56 A-2 H ClH H H *  57 A-2 H H F H H *  58 A-2 F H H OCF₃ H **  59 A-2 H H H H H ** 60 A-2 H H OCHF₂ H H *  61 A-2 H F H H H *  62 A-2 F H H Br H *  63 A-2F H F H H *  64 A-2 Cl H F H H *  65 A-2 H H F H H 211-213  66 A-2 F H HCF₃ H *  67 A-2 Cl H H OCF₃ H *  68 A-2 F CF₃ H H H *  70 A-2 F H H ClH *  71 A-2 F H F H H 226-228  72 A-2 F H H H H *  73 A-2 H H OCF₃ H H * 74 A-2 H CF₃ F H H *  75 A-2 H H OCH₃ H H *  76 A-2 H H CF₃ H H *  77A-2 Cl H Cl H H *  78 A-2 F H F F H *  79 A-2 F H CF₃ H H *  80 A-2 F FF H H *  81 A-2 H H H H H 241-243  82 A-2 H F F H H *  83 A-2 H OCH₃ H HH *  84 A-2 H H CH₃ H H *  85 A-2 F H Br H H *  86 A-2 H CH₂CH₂O H H * 87 A-4 H H F H H *  88 A-2 F H H F H *  89 A-2 F F H H H *  90 A-2 CH₃H cyano H H *  91 A-2 CH₃ H Br H H *  92 A-2 H Br F H H *  93 A-2 H Br HCF₃ H *  94 A-2 F H cyano H H *  95 A-2 F H OCH₃ H H *  96 A-2 CH₃ H F HH *  97 A-5 H OCF₃ H H H *  98 A-2 H OCH₂O H H *  99 A-2 Br H F H H *100 A-4 H H H H H * 101 A-2 H OCH₃ F H H * 102 A-2 H F OCH₃ H H * 103A-7 H Br H OCF₃ H * 104 A-2 H H Br H H * 105 A-2 H H cyano H H * 106 A-2H H Cl H H * 107 A-2 H cyano H H H * 108 A-2 F H F H F * 109 A-6 H H F HH * 123 A-1 H OCH₃ H H H 184-186 124 A-1 H Br H H H 224-226 161CH₂CH₂CH₃ H Br H H H 359 162 CH₂CH₂CH₃ F F H H H 317 163 CH₂CH₂CH₃ F H FH H 317 164 CH₂CH₂CH₃ H H i-Pr H H 323 165 CH₂CH₂CH₃ H H Ph H H 357 166A-1 F H H CF₃ H 456 167 A-2 F H H CF₃ H 434 168 A-1 F H H H F 406 169A-1 H Cl H Cl H 438 170 A-9 H H H H H 208-210 171 A-3 F H cyano H H *172  A-10 F H F H H 365 173 A-1 F H H Cl H 422 174  A-11 H H H H H 404175  A-11 H H F H H 422 176  A-11 F H F H H 440 177  A-11 H CF₃ H H H472 178  A-12 H H H H H 354 179 A-1 H OCH₃ H Br H 478 180 A-1 H OCH₃ H HF 418 181  A-13 H H H H H 384 182  A-13 H H F H H 402 183  A-13 F H F HH 420 184  A-13 H CF₃ H H H 452 185 A-1 H OCH₃ H OCH₃ H 430 186 A-1 HCF₃ H CF₃ H 506 187 A-3 H CF₃ H CF₃ H 429 188 A-3 H CF₃ H Br H 439 189CH₂CF₃ H CF₃ H Br H 189-190 190  A-14 H H H H H 354 191  A-14 H H F H H372 192 A-1 F OCH₃ H H H 418 193 A-1 H OCF₃ H H F 472 194  A-15 H H H HH 370 195  A-15 H H F H H 388 196  A-16 H H H H H 334 197  A-16 H H F HH 175-177 198 A-2 H OCH₃ H OCH₃ H 424 199 CH₂CF₃ H OCH₃ H OCH₃ H 381 200A-1 OCH₃ H H H H 400 201 A-1 OCH₃ H OCH₃ H H 430 202  A-17 H OCH₃ H OCH₃H 408 203  A-17 H CF₃ H H H 416 204  A-17 F H F F H 215-217 205CH₂CF═CH₂ H H F H H 315 206 CH₂CF═CH₂ H OCF₃ H H H 381 207  A-17 H Hcyano H H 373 208  A-17 H OCH₃ H H H 378 209 CH₂CF₃ F OCH₃ H H H * 210A-2 F OCH₃ H H H 412 211  A-18 H H H H H 384 212  A-18 H H F H H 402 213 A-19 H H H H H 333 214  A-19 H H F H H 210-211 215 A-1 H CF₃ H F H 456216 CH(CH₃)CF₃ H H F H H 353 217 CH(CH₃)CF₃ H OCF₃ H H H 419 218  A-20 HH H H H 350 219  A-20 H H F H H 368 220  A-21 H H H H H 336 221  A-21 HH F H H 354 222 CH(CH₃)CF₃ F H F H H 371 223 CH₂CF₃ F H cyano H H 364224  A-16 F H H H H 352 225  A-17 F H H H H 366 226  A-17 H OCF₃ H H H432 227 CH₂CHFCF₂Cl H H F H H 387 228 CH₂CHFCF₂Cl F H F H H 405 229 A-18 F H H H H * 230  A-19 H H cyano H H 358 231  A-19 F H F H H 369232  A-19 H OCF₃ H H H 417 233  A-19 F H H H H 431 234  A-19 OCH₃ H H HH 363 235 A-2 OCH₃ H H Br H 474 236 A-2 Cl H H CF₃ H 466 237 CH(CH₃)CF₃F H H H H 353 238  A-19 F H H CF₃ H 419 239  A-19 F H cyano H H 376 240CH(CH₃)CF₃ H Br H H H 353 241  A-22 H H H H H 335 242 CH(CH₃)CF₃ H Br HCF₃ H 481 243 CH(CH₃)CF₃ H OCH₃ H H H 365 244 CH(CH₃)CF₃ OCH₃ H H H H365 245 A-1 H SF₅ H H Cl 530 246 A-2 OCH₃ H H CF₃ H 549 247 A-2 OCH₃ H HCl H 428 248  A-23 H OCF₃ H H H 438 249  A-17 OCH₃ H H H H 378 250 A-2CH₃ H CH₃ H CH₃ 406 251 A-1 CH₃ H CH₃ H CH₃ 412 252 CH(CH₃)CF₃ Cl H HOCF₃ H 453 253 CH(CH₃)CF₃ H Br H OCF₃ H 497 254 A-2 H SF₅ H H H 490 255CH₂CF₃ H SF₅ H H H 447 256  A-19 H Br H OCF₃ H 495 257  A-24 F H H H H380 258  A-24 OCH₃ H H H H 392 259  A-24 H OCF₃ H H H 446 260  A-24 F HF H H 398 261 A-6 H Br H CF₃ H 524 262 A-6 OCH₃ H H H H 408 263 A-1 HSF₅ H H H 497 264  A-17 Cl H H OCF₃ H 466 265  A-25 H H H H H 181-183266  A-17 F CF₃ H H H 434 267  A-25 H OCF₃ H H H 431 268  A-17 OCF₃ H HH H 432 269  A-17 CF₃ H H H H 416 270 A-1 OCF₃ H H H H 454 271 A-1 CF₃ HH H H 438 272 A-6 H OCF₃ H H H 462 273 A-6 F H H H H 396 274 A-1 I H H HH 496 275 A-1 H I H H H 496 276 A-1 H Br OCH₃ H H 478 277 A-1 OCH₃ H HBr H 478 278 CH₂CH₃ H H H H H 267 279 CH₂CH(CH₃)₂ H H H H H 295 280CH₂CH₂CH₃ F H H H H 299 281 CH₂CH₂CH₃ H H F H H 299 282 CH₂CH₂CH₃ Hcyano H H H 306 283 CH₂CH₂CH₃ cyano H H H H 306 284 CH₂CH₂CH₃ H F H H H299 285 CH₂CH₂CH₃ CH₃ H H H H 295 286 CH₂CH₂CH₃ H H CH₃ H H 295 287CH₂CH₂CH₃ H CF₃ H CF₃ H 417 288 CH₂CH₂CH₃ H H CF₃ H H 349 289 CH₂CH₂CH₃H CH₃ H H H 295 290 CH₂CH₂CH₂CH₃ H H H H H 295 291 CH₂CH₂OCH₃ H H H H H297 292 CH₂CH₂CH₃ OCH₃ H H H H 311 293 CH₂CH₂CH₃ H H OCH₃ H H 311 294CH₂CH₂CH₃ H H Cl H H 315 295 CH₂CH₂CH₃ H OCH₃ H H H 311 296 CH₂CO₂Et H HH H H 325 297 CH(CH₃)₂ H H H H H 281 298 CH₂CH₂CH₃ H F F F H 335 299CH₂(CH₂)₃CH₃ H H H H H 309 300 CH₂CH₂CH₃ H nitro H H H 326 301 CH₂CH₂CH₃H Cl H H H 315 302 CH₂CH₂CH₃ H H OCF₃ H H 365 303 CH₂CH₂CH₃ H NHAc H H H338 304 CH₂CO₂CH₃ H H H H H 311 305 CH₂CH₂CH₃ H CHO H H H 309 306CH₂CH₂CH₃ H Ac H H H 323 307 CH₂CH₂CH₃ H CO₂Et H H H 353 308 CH₂CH₂CH₃CF₃ H H H H ** 349 309 CH₂CH₂CH₃ F H H F H 317 310 CH₂CH₂CH₃ H Cl H Cl H349 311 CH₂CF₃ H H CF₃ H H 389 312 CH₂CF₃ H CF₃ H CF₃ H 457 313 CH₂CF₃ HF H F H 357 314 CH₂CH₂CH₃ F H H Br H 377 315 CH₂CH₂CH₃ H OCH₃ H Br H 389316 CH₂CH₂CH₃ H OCH₃ OCH₃ H H 341 317 CH₂CH₂CH₃ OCH₃ H H F H 329 318CH₂CH₂CH₃ OCH₃ H H Cl H 345 319 CH₂CH₂CH₃ F CH₃ H Cl H 347 320 CH₂CF₃ HOCH₃ H Br H 429 321 CH₂CF₃ CF₃ H H H H 389 322 CH₂CH₂CH₃ OCF₃ H H H H365 323 CH₂CF₃ OCF₃ H H H H 405 324 CH₂CF₃ H H OCF₃ H H 405 325 CH₂CF₃ HH cyano H H 346 326 CH₂CH₂CH₃ OCH₃ OCH₃ H H H 341 327 A-8 H H H H H 383328 CH₂CF₃ H OCH₃ OCH₃ H H 381 329 CH₂CF₃ F CH₃ H Cl H 387 330 CH₂CF₃ FF H H H 357 331 CH₂CH₂CH₃ H H SCH₃ H H 327 332 CH₂CH₂CH₃ H OCH₃ Cl H F363 333 CH₂CH₂CH₃ H H t-Bu H H 337 334 CH₂CH₂CH₃ NHCOt-Bu H H CH₃ H 394335 CH₂CH₂CH₃ H H SO₂Me H H 359 336 CH₂CF₃ H OCH₃ Cl H F 403 337CH₂CH₂CH₃ H CF₃ OCH₃ H H 379 338 CH₂CF₃ H CF₃ OCH₃ H H 419 339 CH₂CH₂CH₃H n-Bu H H H 337 340 CH₂CH₂CH₃ F H CF₃ H H 367 341 CH₂CH₂CH₃ H OCF₃ H HF 383 342 CH₂CH₂CH₃ H H CO₂Et H H 353 343 CH₂CH₂CH₃ H CH₃ H CH₃ H 309344 CH₂CH₂CH₃ OCH₃ H H CF₃ H 379 345 CH₂CH₂CH₃ OCH₂CH₃ H H CF₃ H * 346CH₂CF₃ OCH₂CH₃ H H CF₃ H * 347 CH₂CH₂CH₃ F CF₃ H H H 367 348 CH₂CH₂CH₃OCH₃ Br H CH₃ H * 349 CH₂CH₂CH₃ CH₃ H H CH₃ H * 350 CH₂CF₃ F CF₃ H H H407 351 A-8 H H cyano H H * 352 CH₂CF₃ F H H F H * 353 CH₂CF₃ H Cl F H H373 354 CH₂CF₃ H H n-Bu H H 377 355 CH₂CF₃ H CF₃ F H H 407 356 CH₂CF₃ HF cyano H H 338 357 CH₂CF₃ Cl H F H H 373 358 CH₂CF₃ OCH₃ H F H H 368359 CH₂CF₃ OCH₃ H H CF₃ H 419 360 CH₂CF₃ H F H H H 339 361 CH₂CF₃ H HCH₃ H H 335 362 CH₂CF₃ H H OCH₃ H H 351 363 CH₂CF₃ H CH₃ H H H 335 364CH₂CF₃ H H Br H H 399 365 CH₂CH₂CF₃ H H F H H 353 366 CH₂CH₂CF═CF₂ H H FH H 365 367 CH₂CH₂CF═CF₂ H OCF₃ H H H 431 368 CH₂CH₂CF═CF₂ F H F H H 383369 CH₂CF₃ H cyano F H H * 370 CH₂CF₂CF₃ H CF₃ H H H 439 371CH₂CH₂CF═CF₂ H CF₃ H H H 415 372 A-8 H CF₃ H H H 451 373 CH₂CH₂CF═CF₂ ClH Cl H H 415 374 A-8 Cl H Cl H H 451 375 CH₂CF₂CF₃ Cl H Cl H H 439 376CH₂CF₃ CH₃ H H H H 335 377 CH₂CF₃ Br H H H H 399 378 CH₂CF₃ Cl H H H H355 379 CH₂CF₃ H n-Bu I H H 503 380 CH₂CF₃ H n-Bu H H H 377 381 CH₂CF₃Cl H Cl H Cl 423 382 CH₂CH₂CF═CF₂ Cl H Cl H Cl 449 383 A-8 Cl H Cl H Cl485 384 CH₂CF₃ Cl H H H Cl 389 385 CH₂CF₃ CH₃ H CH₃ H H 349 386 CH₂CF₃ Hcyano H H H 346 387 CH₂CF₃ n-Bu H H H H 377 388 CH₂CF₂CF₃ Cl H Cl H Cl473 389  A-26 H H F H H 383 390  A-26 F H F H H 401 391  A-26 H OCF₃ H HH 449 392 CH₂CF₃ F F F H H 375 393 CH₂CF₃ F H F F H 375 394 CH₂CF₃ F H FH F 375 395 CH₂CF₃ H F F F H 375 396 CH₂CF₃ CF₃ H F H H 407 397 CH₂CF₃ HOCF₃ H H Cl 439 398 CH₂CF₃ H CHO F H H 367 399 CH₂CF₃ cyano H H H H 346400 CH₂CH₂CH₃ H Br F H H 377 401 CH₂CH₂CH₃ H CF₃ F H H 367 402 CH₂CO₂CH₃H H F H H 329 403 CH₂CF₃ F H Br H H 417 404 CH₂CF₃ F H F H Br 435 405CH₂CH₂CH₃ H F F H H 317 406 CH₂CH₂CH₃ H Cl F H H 333 407 CH₂CH₂CH₃ Cl HF H H 333 408 CH₂CH₂CH₃ F H F H H 317 409 CH₂CH₂CH₃ OCH₃ H F H H 329 410A-8 H cyano F H H 426 411 A-7 H OCF₃ H H H 414 412 A-7 H H F H H 348 413A-7 F H F H H 365 414 A-7 H H H H H 330 415 A-2 CF₃ H F H H 450 416 A-34 H H H H H * 417 A-2 H H SCH₃ H H 410 418 A-2 H Cl H Cl H * 419 A-2Cl H F H H 398 420 A-2 CH₃ H H H H 378 421 A-2 OCF₃ H H H H 448 422 A-2cyano H H H H 389 423 A-2 OCH₃ H H H H 394 424 A-3 H OCH₃ H H H 323 425A-2 H SCH₃ H H H * 426 CH₂CF₃ H nitro H H H * 427 A-2 H Si(CH₃)₃ H H H *428 A-27 H H H H H 323 429 A-27 F H F H H 359 430 A-2 H H Si(CH₃)₃ H H *431 CH₂CF₃ H OCH₂O H H 365 432 CH₂CF₃ H OH H H H 337 433 CH₂CF₃ CH₃ H FH H * 434 CH₂CF₃ H OAc H H H 379 435 CH₂CF₃ H CH₂CH₂O H H 363 436 A-4 HOCF₃ H H H * 437 A-4 F H F H H 434 438 CH₂CF₃ H OCF₂O H H 401 439  A-27H H F H H 341 440 A-2 H CF₃ H CF₃ H 500 441 A-2 H nitro H H H 409 442A-2 OCH₃ H OCH₃ H H 424 443 A-4 H H OCH₃ H H * 444 A-4 F H H H H 416 445A-2 H CF₃ OCH₃ H H 462 446 A-2 H OCF₂O H H 444 447 A-2 H OAc H H H 422448 A-2 F F OCH₃ H H 430 449 A-5 H H F H H 363 450 A-5 H H H H H 345 451 A-28 H H F H H 416 452  A-29 H H H H H 398 453  A-28 H OCF₃ H H H * 454 A-29 H H F H H 416 455  A-29 F H F H H 434 456  A-30 H H H H H 355 457 A-30 H H F H H 373 458  A-30 F H F H H 391 459 A-2 H OCH₂CF₃ H H H *460 A-6 H H H H H 378 461 A-2 F H H H F 400 462  A-17 F H cyano H H 391463  A-31 H H H H H 344 464  A-31 H H F H H 362 465  A-31 F H F H H 380466  A-32 H H H H H 323 467  A-32 H H F H H 341 468  A-32 F H F H H 359469 A-1 F H cyano H H 413 470  A-33 H H H H H 408 471  A-33 H H F H H426 472  A-33 F H F H H 444 473 A-1 H CF₃ F H H 455 474 A-1 Cl H F H H422 475 A-1 H H cyano H H 395 476 A-2 H F H F H 400 477 A-1 H F H H H388 478 A-1 H H CF₃ H H 438 479 A-1 H H OCF₃ H H 454 480 A-1 H H CH₃ H H384 481 A-1 cyano H H H H 395 482 A-1 H F F H H 406 483  A-10 H H F HH * 484  A-10 H OCF₃ H H H 413 485  A-10 H H H H H 329 486 A-1 H OCH₃ FH H * 487 A-1 Br H F H H 466 488 A-1 CH₃ H cyano H H 409 489 A-1 Cl H ClH H 438 490 A-1 H OCF₃ H H Cl 488 491 A-1 H OCF₃ H Br H 209-210 492 A-1F F F H H 196-198 424 493 A-1 F H F F H 195-197 424 494 A-1 H OCH₂O HH >250 414 495 A-1 H CH₂CH₂O H H 188-190 412 496 A-1 F H H Br H 466 497A-6 F H F H H 414 498 A-1 H CF₃ H Br H 188-190 516 499 A-1 H F H F H 406500 A-1 H F OCH₃ H H 205-207 418 501 A-1 F H F H F * 502  A-33 H OCF₃ HH H 153-155 504 503  A-33 H OCH₃ H H H 438 604  A-35 H H H H H 330 605 A-36 H H H H H 330 606  A-35 H H F H H * 618 A-1 F F H H F 424 619 A-1H CF₃ H Cl F 490 621 A-2 H SF₅ H H Cl 524 622 A-1 H OCF₃ H Cl H 488 623 A-37 F H H H H 432 624  A-37 H H F H H 432 625  A-37 H OCF₃ H H H 498627  A-37 H CF₃ H Br H 560 629 CH₂CO₂H H H H H H 297 631  A-38 H H H H H335 632 A-2 I H H H H 490 634 A-1 H CF₃ H Cl H 472 642  A-40 F H F H H159-160 648  A-40 OCH₃ H H H H * 649 CH₂CH₂CH(OMe)₂ H H H H H 341 650CH₂CH(OMe)₂ H H H H H 327 651 A-2 F F H H F 418 652 A-2 H CF₃ H Cl F 484654 A-1 F H OCH₃ H H 418 663 A-1 F Cl H H F 440 664 A-1 OCH₃ H H F F 436665 A-2 OCH₃ H H F F 430 666 A-2 F Cl H H F 434 673  A-41 H H H H H 360674  A-41 F H H H H 378 675  A-40 F H H H H 365 676  A-41 H H F H H 378677  A-17 H H F H H 372 678  A-41 F H F H H 396 679  A-41 H OCF₃ H H H444 720 CH₂CF₃ H H SF₅ H H 447 721 A-1 H H SF₅ H H 496 722 A-2 H H SF₅ HH 490 737  A-37 H Br H OCF₃ H 576 740 A-2 OCH₃ F H F H 430 741 A-2 FOCH₃ H H F 430 742 A-1 OCH₃ F H F H 436 743 A-1 F OCH₃ H H F 436 744 A-2F H H OCH₃ H 412 745 CH₂CF₃ F H H OCH₃ H 369 746 A-17 F F H H H 384 *See Index Table G for ¹H NMR data. ** See synthesis example for ¹H NMRdata.

INDEX TABLE B

Compound R¹ R² m.p. (° C.) AP+ (M + 1) 110 Br CH₂CH₂CH₃ * 111 I CH₂CF₃ *112 I CH₂CH₂CH₃ * 113 I A-8 * 114 I CH₂CF₂CF₃ * 115 CH(CH₃)₂ CH₂CF₃ *116 CH₂CH(CH₃)₂ CH₂CF₃ * 117 CH₂CH₂CF═CF₂ CH₂CF₃ * 118 I A-2 ** 125 HA-1 ** 119 6-fluoro-3-pyridinyl A-2 * 120 6-chloro-3-pyridinyl A-2 * 1213-chloro-4-pyridinyl CH₂CF₃ 248-249 521 4-trifluoromethyl-2-pyridinylCH₂CF₃ * 522 4-trifluoromethyl-2-pyridinyl A-17 417 5372-bromo-4-pyridinyl A-2 443 540 2-bromo-4-pyridinyl A-1 449 5476-trifluoromethyl-2-pyridinyl A-17 * 550 2-cyano-4-pyridinyl A-1 396 5522-pyridinyl CH₂CH₂CH₃ 282 553 3-pyridinyl CH₂CH₂CH₃ 282 554 phenylCH₂CO₂CH(CH₃)₂ 339 555 2-naphthalenyl CH₂CH₂CH₃ 331 556 1-naphthalenylCH₂CH₂CH₃ 331 561 4-pyridinyl CH₂CH₂CH₃ 282 562 2-chloro-4-pyridinylCH₂CH₂CH₃ 316 564 4-fluoro-1-naphthalenyl CH₂CH₂CH₃ * 5706-chloro-3-pyridinyl CH₂CF₃ 356 571 6-fluoro-3-pyridinyl CH₂CF₃ 340 5734-fluoro-1-naphthalenyl A-2 432 574 6-methoxy-2-naphthalenyl A-2 444 5756-methoxy-3-pyridinyl A-2 395 576 5-fluoro-2-pyridinyl A-2 383 5775-trifluoromethyl-3-pyridinyl A-2 433 579 2-fluoro-3-pyridinyl A-2 383584 3-fluoro-4-pyridinyl A-2 383 585 5-methoxy-2-pyridinyl A-2 395 5863-fluoro-2-pyridinyl A-2 383 587 3-chloro-2-pyridinyl A-2 399 5914-trifluoromethyl-2-pyridinyl A-2 433 593 6-trifluoromethyl-2-pyridinylA-2 433 597 4-trifluoromethyl-2-pyridinyl A-1 225-227 439 5982-chloro-4-pyridinyl A-1 242-243 405 600 6-trifluoromethyl-2-pyridinylA-1 * 608 I A-1 ** 609 H CH₂CH₂CH₃ ** 610 H CH₂CF₃ 214-215 611 H A-2 **612 H A-7 * 628 2-bromo-4-pyridinyl A-37 493 636 2-methoxy-4-pyridinylA-1 401 637 C(═NOCH₃)CF₃ CH₂CF₃ ** 638 C(═NOCH₂CH₃)CF₃ CH₂CF₃ * 6532-trifluoromethyl-4-pyridinyl A-1 439 656 C(═NOCH₂CHMe₂)CF₃ CH₂CF₃ * 657C(═NOCMe₃)CF₃ CH₂CF₃ * 658 C(═NOCH₂CMe₃)CF₃ CH₂CF₃ * 659C(═NOCH₂CO₂Et)CF₃ CH₂CF₃ * 660 C(O)NHphenyl A-1 413 661C(O)NH(3-methoxyphenyl) A-1 443 687 C(O)OEt CH₂CH₂CH₃ 277 688C(O)NH(4-fluorophenyl) CH₂CH₂CH₃ 342 689 C(O)NH(2-chlorophenyl)CH₂CH₂CH₃ 358 690 C(O)NH(3-chlorophenyl) CH₂CH₂CH₃ 358 691C(O)NH(4-chlorophenyl) CH₂CH₂CH₃ 358 692 C(O)NHphenyl CH₂CH₂CH₃ 324 693C(O)O(4-nitrophenyl) CH₂CH₂CH₃ 370 694 C(O)phenyl CH₂CH₂CH₃ 309 695C(O)(2-fluorophenyl) CH₂CH₂CH₃ 327 696 C(O)(3-fluorophenyl) CH₂CH₂CH₃327 697 C(O)(4-fluorophenyl) CH₂CH₂CH₃ 327 698 C(O)(2-methylphenyl)CH₂CH₂CH₃ 323 699 C(O)(3-methylphenyl) CH₂CH₂CH₃ 323 700 C(O)OEt A-1 *701 C(O)phenyl A-1 * 702 C(O)CF₃ A-1 236-238 703 C(O)(4-fluorophenyl)A-1 235-237 704 C(O)(3-fluorophenyl) A-1 226-228 706C(O)(2-fluorophenyl) A-1 190-192 707 C(O)[3-(trifluoromethyl)phenyl] A-1225-226 708 C(O)(2-thienyl) A-1 214-216 709C(O)[4-(trifluoromethyl)phenyl] A-1 242-243 710 C(O)CH₃ A-1 183-185 711C(O)CF₃ CH₂CF₃ 202-203 712 C(O)CF₃ A-2 209-210 713 C(O)CF₂CF₃ A-1204-205 714 C(O)CF₂CF₃ A-2 189-190 715 C(O)CF₂CF₂CF₃ A-1 156-157 716C(O)CF₂CF₂CF₃ A-2 134-135 729 C(═NOC(CH₃)₃)H CH₂CF₃ * 730 C(═NOCH₂CH₃)HCH₂CF₃ * 731 C(═NOCH₂C(CH₃)₃)H CH₂CF₃ * 758 C(═NOCH₃)H CH₂CF₃ * 759C(═NOCH₂Ph)H CH₂CF₃ * * See Index Table G for ¹H NMR data. ** Seesynthesis example for ¹H NMR data.

INDEX TABLE C

Compound R^(a) R² m.p. (° C.) AP+ (M + 1) 523 3-(3-pyridinyl) A-2 441524 3-(6-chloro-3-pyridinyl) A-2 474 525 3-(6-fluoro-3-pyridinyl) A-2459 527 3-(6-fluoro-3-pyridinyl), 6-fluoro A-2 477 5284-(6-chloro-3-pyridinyl) A-2 475 529 3-(6-methoxy-3-pyridinyl) A-2 471530 3-(6-chloro-3-pyridinyl) A-1 481 531 3-(6-fluoro-3-pyridinyl), A-2527 5-trifluoromethyl 534 3-(6-chloro-3-pyridinyl) CH(CH₃)CF₃ 446 5363-(6-fluoro-3-pyridinyl), 4-fluoro A-2 539 3-(6-chloro-3-pyridinyl),6-methoxy A-2 505 541 3-(6-chloro-3-pyridinyl), 4-fluoro A-1 499 5423-(6-fluoro-3-pyridinyl) A-1 465 543 3-(6-chloro-3-pyridinyl), A-1 5495-trifluoromethyl 544 3-(6-fluoro-3-pyridinyl), A-1 5335-trifluoromethyl 545 3-(6-fluoro-3-pyridinyl) A-19 428 5463-(6-fluoro-3-pyridinyl) A-6 473 549 3-(6-fluoro-3-pyridinyl), A-1 5495-trifluoromethoxy 551 2-(6-chloro-3-pyridinyl) A-1 481 557 3-phenylCH₂CH₂CH₃ 357 558 4-phenoxy CH₂CH₂CH₃ 373 559 2-phenoxy CH₂CH₂CH₃ 373560 2-phenyl CH₂CH₂CH₃ 357 563 3-phenoxy CH₂CH₂CH₃ 373 565 3-benzyloxyCH₂CH₂CH₃ 387 566 3-benzyloxy CH₂CF₃ 178-179 427 567 4-benzyloxy CH₂CF₃203-204 427 568 2-benzyloxy CH₂CF₃ 165-166 427 578 2-(B-1), 4-fluoroCH₂CF₃ 480 580 3-(B-2) CH₂CF₃ 223-225 428 581 3-(B-1) CH₂CF₃ 462 5823-(B-1) A-2 505 594 3-(B-3), 4-fluoro A-2 446 595 3-(B-3), 4-fluoroCH₂CF₃ 446 596 3-(B-4) CH₂CF₃ 170-172 462 616 3-(6-bromo-3-pyridinyl)A-1 525 617 3-(6-trifluoromethyl-3-pyridinyl) A-1 515 6263-(6-chloro-3-pyridinyl) A-37 525 635 3-(6-chloro-3-pyridinyl), A-1 5655-trifluoromethoxy 655 3-(6-chloro-3-pyridinyl), 5-methoxy A-1 511 6823-(6-trifluoromethyl-3-pyridinyl), A-1 599 5-trifluoromethoxy 6843-(6-trifluoromethyl-3-pyridinyl), A-1 583 5-trifluoromethyl 6853-(6-trifluoromethyl-3-pyridinyl), A-1 545 4-methoxy 7173-(6-chloro-3-pyridinyl), 4-methoxy A-1 511 7343-(6-trifluoromethyl-3-pyridinyl) A-17 493 7353-(6-trifluoromethyl-3-pyridinyl) A-2 509 7363-(6-trifluoromethyl-3-pyridinyl) A-37 559 7383-(6-trifluoromethyl-3-pyridinyl), A-1 533 6-fluoro 7393-(6-trifluoromethyl-3-pyridinyl), A-37 577 6-fluoro

INDEX TABLE D

AP+ m.p. (M + Cmpd R² R^(a) R^(b) R^(c) R^(d) R^(e) (° C.) 1) 126CH₂CH₂CH₃ H H H H H 161-168 127 CH₂CH₂CH₃ F H H H Cl 216-219 128CH₂CH₂CH₃ H Cl H Cl H 180-183 129 CH₂CH₂CH₃ Cl Cl H H H 188-192 130CH₂CH₂CH₃ F H H H F 207-210 131 CH₂CH₂CH₃ CH₃ H H H H 223-225 132CH₂CH₂CH₃ H H i-Pr H H * 133 CH₂CF₃ F H F H H * 134 CH₂CF₃ H H H H H *135 CH₂CF₃ H OCF₃ H H H * 136 A-2 H H H H H * 137 A-2 H H F H H * 138A-2 H OCF₃ H H H ** 139 A-1 H H H H H * 140 A-1 H H F H H * 141 A-1 HOCF₃ H H H * 142 CH₂CH₂CH₃ F H F H H * 143 CH₂CH₂CH₃ H H Ph H H 363 144CH₂CO₂CH₂CH₃ H H H H H 331 145 A-1 H OCF₃ H Br H 538 146 A-1 F H F H H412 147 A-1 H OCH₃ H H H * 148 A-1 F H H Cl H 428 149 A-2 H OCH₃ H H H400 150 A-2 H OCH₃ H OCH₃ H 430 151 A-2 F H F H H 406 152 A-1 F H H CF₃H * 153 A-2 F H H CF₃ H 456 154 A-2 F H H Cl H 422 155 A-2 H OCF₃ H Br H532 156 A-1 H OCH₃ H OCH₃ H 436 157 A-2 F H H H H 216-218 388 158 A-2OCH₃ H H H H  99-100 159 A-1 F H H H H 192-194 160 A-1 OCH₃ H H H H *630 A-17 H H H H H 223-225 633 A-2 I H H H H 496 639 A-17 H OCF₃ H H H *640 A-39 H OCF₃ H H H 147-149 641 A-17 F H F H H 235-237 643 A-17 F H HH H 223-225 644 A-39 F H H H H 169-171 645 A-39 H H H H H 190-192 646A-17 OCH₃ H H H H * 647 A-39 OCH₃ H H H H * 747 A-17 H OCH₃ H H H 384748 A-2 F F H H H 406 749 A-1 F F H H H 412 750 A-17 F F H H H 390 * SeeIndex Table G for ¹H NMR data. ** See synthesis example for ¹H NMR data.

INDEX TABLE E

Cmpd R¹ R² R³ ** R⁴ ** m.p. (° C.) AP+ (M + 1) 504 phenyl A-2 CH₃ phenyl404 505 phenyl A-2 phenyl CH₃ 404 506 4-fluorophenyl A-2 CH₃ phenyl 422507 phenyl CH₂CF₃ phenyl CH₃ 361 508 4-fluorophenyl CH₂CF₃ phenyl CH₃379 509 phenyl CH₂CH₂CH₃ CH₃ CH₃ 259 510 4-fluorophenyl CH₂CH₂CH₃ CH₃CH₃ 276 511 phenyl A-2 CH₃ CH₃ * 512 phenyl CH₂CF₃ CH₃ CH₃ 299 5134-fluorophenyl A-2 CH₃ CH₃ 360 514 phenyl A-1 CH₃ CH₃ 222-224 388 5153-(trifluoromethoxy)- CH₂CH₂CH₃ CH₂CH₂CH₂CH₂ 369 phenyl 5164-fluorophenyl CH₂CH₂CH₃ CH₂CH₂CH₂CH₂ 303 517 phenyl A-2

354 518 3-(trifluoromethoxy)- phenyl A-2

* 519 phenyl CH₂CH₂CH₃

284 588 4-fluorophenyl A-2

400 589 3-(trifluoromethoxy)- phenyl A-2

466 590 2,4-difluorophenyl A-2

418 592 phenyl A-2

382 667 2-fluorophenyl A-1

406 668 2-fluorophenyl A-2

400 669 2-methoxyphenyl A-2

412 670 2-methoxyphenyl A-1

418 671 4-fluorophenyl A-1

406 672 3-(trifluoromethoxy)- phenyl A-1

472 683 3-bromo- 5-(trifluoromethoxy) phenyl A-1

550 718 2-fluorophenyl A-2 CH₃ CH₃ 249-252 360 719 2-fluorophenyl A-1CH₃ CH₃ 190-193 366 751 2-fluorophenyl A-2

450 752 4-fluorophenyl A-2

450 753 3-(trifluoromethoxy)- phenyl A-2

516 754 3-(trifluoromethoxy)- phenyl A-1

522 755 2-fluorophenyl A-1

456 756 4-fluorophenyl A-1

456 * See Index Table G for ¹H NMR data. ** When R³ and R⁴ are takentogether with the contiguous linking nitrogen and carbon atoms to form aring, the wavy line indicates that the ring is attached to the remainderof the molecule with the orientation shown below.

INDEX TABLE F m.p. AP+ Cmpd Structure (° C.) (M + 1) 520

442 526

520 532

588 533

538 535

538 538

476 548

482 569

* 572

413 583

* 599

* 601

* 602

438 603

504 613

** 614

492 615

366 705

438 732

626 733

642 757

404 * See Index Table G for ¹H NMR data. ** See synthesis example for ¹HNMR data.

INDEX TABLE G Cmpd No. ¹H NMR Data ^(a, b) 3 δ (acetone-d₆) 9.5 (m, 1H),8.5 (m, 1H), 8.1 (m, 1H), 7.97 (s, 1H), 7.75 (dd, 1H), 7.69 (m, 1H),7.31 (t, 1H), 7.15 (m, 1H), 5.35 (br s, 2H). 8 δ 9.51 (d, 1H), 8.09 (m,1H), 7.85-7.69 (m, 2H), 7.45 (d, 1H), 7.38 (t, 1H), 7.32 (t, 1H), 7.07(d, 1H), 4.29 (t, 2H), 1.87-1.75 (m, 2H), 1.08 (t, 3H). 9 δ 9.57 (d,1H), 8.23 (t, 1H), 7.61 (d, 1H), 7.49 (t, 2H), 7.41 (d, 1H), 7.29 (d,1H), 5.2 (br s, 2H). 10 δ 9.57 (d, 1H), 8.23 (t, 1H), 7.61 (d, 1H), 7.49(m, 2H), 6.8-6.95 (m, 2H), 5.2 (br s, 2H). 12 δ 9.52 (dd, 1H), 8.15-8.07(m, 2H), 8.03-7.98 (m, 1H), 7.47 (t, 3H), 7.34 (m, 1H), 4.30 (t, 2H),1.91-1.74 (m, 2H), 1.09 (t, 3H). 14 δ 9.58 (d, 1H), 8.23 (t, 1H), 7.61(d, 1H), 7.51 (t, 1H), 7.48 (d, 1H), 7.14 (m, 2H). 15 δ 9.60 (d, 1H),8.23 (t, 1H), 7.75 (d, 2H), 7.59 (d, 1H), 7.51 (t, 2H), 7.24 (m, 2H). 17δ (acetone-d₆) 9.45 (d, 1H), 8.45 (m, 1H), 8.1 (d, 1H), 7.63 (t, 1H),7.3 (d, 1H), 7.22 (m, 1H), 7.95 (dd, 1H), 6.9 (t, 1H), 5.35 (br s, 2H),3.73 (s, 3H). 18 δ 9.5 (m, 1H), 8.1 (m, 1H), 7.75 (m, 2H), 7.63 (dd,1H), 7.4-7.3 (m, 2H), 7.05 (m, 1H), 4.30 (m, 2H), 1.2 (m, 1H), 0.62 (m,4H). 20 δ 9.51 (dd, 1H), 8.12 (ddd, 2H), 7.51-7.42 (m, 3H), 7.38-7.31(m, 1H), 6.72-6.60 (m, 1H), 4.29 (t, 2H), 1.93-1.68 (m, 2H), 1.09 (t,3H). 21 δ 9.56 (d, 1H), 8.23 (t, 1H), 7.59 (d, 1H), 7.49 (m, 2H), 7.16(t, 2H), 5.2 (br s, 2H). 22 δ 9.57 (d, 1H), 8.19 (t, 1H), 7.78 (dd, 1H),7.67 (dd, 1H), 7.35-7.55 (m, 3H), 7.09 (d, 1H), 4.7-5.05 (m, 2H), 4.37(m, 1H), 2.2-2.55 (m, 2H). 25 δ 9.57 (d, 1H), 8.23 (t, 1H), 7.58 (d,1H), 7.46 (t, 2H), 7.38(s, 1H), 6.90 (d, 1H), 3.79 (s, 3H). 27 δ 9.57(d, 1H), 8.17 (t, 1H), 7.74 (m, 2H), 7.49 (d, 1H), 7.41 (t, 1H), 7.08(t, 2H), 4.7-5.05 (m, 2H), 4.37 (m, 1H), 2.2-2.55 (m, 2H). 28 δ 9.53(dd, 1H), 8.07 (ddd, 1H), 7.81-7.72 (m, 2H), 7.45 (d, 1H), 7.42-7.36 (m,2H), 7.31 (m, 1H), 7.25-7.20 (m, 1H), 4.30 (d, 1H), 1.90-1.73 (m, 2H),1.08 (t, 3H). 30 δ 9.54 (d, 1H), 8.21 (t, 1H), 7.51 (m, 2H), 7.42 (t,1H), 6.9 (m, 2H), 4.7-5.05 (m, 2H), 4.37 (m, 1H), 2.2-2.55 (m, 2H). 32 δ9.61 (d, 1H), 8.24 (t, 1H), 7.78 (dd, 1H), 7.67 (d, 1H), 7.50 (t, 1H),7.44 (d, 2H), 6.69 (t, 1H). 33 δ 9.61 (d, 1H), 8.21 (t, 1H), 7.76 (d,1H), 7.71 (s, 1H), 7.55 (dt, 1H), 7.49 (t, 1H), 7.39 (t, 1H), 7.10 (d,1H). 34 δ 9.59 (d, 1H), 8.15 (t, 1H), 7.72 (d, 2H), 7.52 (d, 1H), 7.44(t, 1H), 7.38 (t, 2H), 7.23 (t, 1H), 5.5 (br s, 2H). 35 δ 9.61 (d, 1H),8.21 (t, 1H), 7.73 (m, 2H), 7.56 (d, 1H), 7.49 (t, 1H), 7.08 (t, 2H). 36δ 9.59 (d, 1H), 8.23 (t, 1H), 7.58 (d, 1H), 7.50 (m, 2H), 7.50 (t, 1H),6.85-6.95 (m, 2H). 37 δ 9.57 (d, 1H), 8.13 (t, 1H), 7.74 (d, 2H), 7.49(d, 1H), 7.40 (m, 3H), 7.26 (m, 1H), 4.54 (t, 2H), 2.85 (m, 2H). 38 δ9.58 (d, 1H), 8.16 (t, 1H), 7.74 (d, 2H), 7.49 (d, 1H), 7.40 (t, 3H),7.25 (m, 1H), 4.58 (dd, 2H), 2.85 (m, 2H). 39 δ 9.49 (dd, 1H), 8.03(ddd, 1H), 7.73 (d, 2H), 7.58 (d, 1H), 7.36 (t, 2H), 7.28 (m, 1H), 7.23-7.17 (m, 1H), 4.28 (d, 2H), 1.24-1.09 (m, 1H), 0.69-0.45 (m, 4H). 41 δ9.51 (dd, 1H), 8.13 (ddd, 1H), 8.03-7.97 (m, 2H), 7.68-7.62 (m, 2H),7.48 (d, 1H), 7.39- 7.33 (m, 1H), 4.29 (t, 2H), 1.90-1.72 (m, 2H), 1.09(t, 3H). 42 δ 9.55 (m, 1H), 8.15 (m, 1H), 7.75 (m, 2H), 7.67 (s, 1H),7.6 (dd, 1H), 7.42 (m, 1H), 7.1 (m, 2H), 5.58 (br s, 2H). 44 δ 9.5 (m,1H), 8.15 (m, 1H), 7.65 (s, 1H), 7.6 (dd, 1H), 7.5 (m, 1H), 7.4 (m, 1H),6.9 (m, 2H), 5.55 (br s, 2H). 50 δ (acetone-d₆) 9.4 (m, 1H), 8.45 (m,1H), 8.1 (dd, 1H), 7.95 (s, 1H), 7.6 (m, 1H), 7.55 (m, 1H), 7.3 (m, 1H),7.1 (m, 2H), 5.74 (d, 2H). 51 δ 9.54 (d, 1H), 8.47 (s, 1H), 8.07 (dd,1H), 7.99 (s, 1H), 7.76 (d, 1H), 7.68 (d, 1H), 7.25-7.45 (m, 5H), 5.58(br s, 2H). 52 δ 9.55 (d, 1H), 8.48 (s, 1H), 8.10 (m, 3H), 7.67 (d, 1H),7.48 (s, 1H), 7.42 (m, 2H), 7.36 (d, 1H), 5.59 (br s, 2H). 53 δ 9.56 (d,1H), 8.48 (s, 1H), 8.14 (s, 1H), 8.09 (dd, 1H), 8.07 (d, 1H), 7.69 (dd,1H), 7.51 (m, 2H), 7.40 (m, 2H), 5.6 (br s, 2H). 54 δ 9.56 (d, 1H), 8.47(s, 1H), 8.08 (dd, 1H), 7.81 (d, 1H), 7.77 (s, 1H), 7.68 (dd, 1H),7.3-7.45 (m, 4H), 7.12 (d, 1H), 5.59 (br s, 2H). 55 δ 9.52 (d, 1H), 8.47(s, 1H), 8.10 (dd, 1H), 8.04 (s, 1H), 7.78 (s, 1H), 7.66 (dd, 1H),7.3-7.45 (m, 4H), 5.57 (br s, 2H). 56 δ 9.55 (d, 1H), 8.48 (s, 1H), 8.08(dd, 1H), 7.83 (d, 1H), 7.77 (dd, 1H), 7.3-7.45 (m, 4H), 7.24 (d, 1H),5.59 (br s, 2H). 57 δ 9.56 (d, 1H), 8.48 (s, 1H), 8.05 (dd, 1H), 7.79(d, 1H), 7.77 (dd, 1H), 7.3-7.45 (m, 4H), 7.24 (d, 1H), 5.59 (br s, 2H).59 δ 9.56 (d, 1H), 8.48 (s, 1H), 8.05 (dd, 1H), 7.79 (d, 2H), 7.70 (dd,1H), 7.2-7.45 (m, 6H), 5.59 (br s, 2H). 60 δ 9.56 (d, 1H), 8.48 (s, 1H),8.05 (dd, 1H), 7.81 (d, 2H), 7.69 (dd, 1H), 7.3-7.45 (m, 3H), 7.17 (d,2H), 6.52 (t, 1H), 5.59 (br s, 2H). 61 δ 9.56 (d, 1H), 8.48 (s, 1H),8.08 (dd, 1H), 7.70 (dd, 1H), 7.63 (d, 1H), 7.58 (m, 1H), 7.3- 7.45 (m,4H), 6.95 (td, 1H), 5.58 (br s, 2H). 62 δ 9.51 (d, 1H), 8.48 (s, 1H),8.10 (dd, 1H), 7.10 (m, 2H), 7.3-7.45 (m, 4H), 7.03 (dd, 1H), 5.58 (brs, 2H). 63 δ 9.51 (d, 1H), 8.48 (s, 1H), 8.08 (dd, 1H), 7.69 (ddd, 1H),7.54 (q, 1H), 7.3-7.45 (m, 4H), 6.85-7.0 (m, 2H), 5.57 (br s, 2H). 64 δ9.52 (d, 1H), 8.48 (s, 1H), 8.10 (dd, 1H), 7.70 (d, 1H), 7.48 (dd, 1H),7.42 (m, 2H), 7.34 (d, 1H), 7.25 (d, 1H), 7.06 (td, 1H), 5.59 (br s,2H). 66 δ 9.53 (d, 1H), 8.49 (s, 1H), 8.12 (dd, 1H), 7.90 (d, 1H), 7.69(dd, 1H), 7.65 (m, 1H), 7.2- 7.45 (m, 4H), 5.59 (br s, 2H). 67 δ 9.53(d, 1H), 8.48 (s, 1H), 8.11 (dd, 1H), 7.79 (d, 1H), 7.70 (dd, 1H), 7.51(d, 1H), 7.4 (m, 3H), 7.35 (d, 1H), 7.15 (d, 1H), 5.75 (br d, 1H), 5.4(br d, 1H). 68 δ 9.53 (d, 1H), 8.48 (s, 1H), 8.11 (dd, 1H), 7.79 (t,1H), 7.69 (dd, 1H), 7.25-7.45 (m, 4H), 5.58 (br s, 2H). 70 δ 9.52 (d,1H), 8.49 (s, 1H), 8.10 (dd, 1H), 7.69 (dd, 1H), 7.56 (dd, 1H), 7.4 (m,2H), 7.09 (t, 1H), 5.58 (br s, 2H). 72 δ 9.50 (d, 1H), 8.47 (s, 1H),8.03 (dd, 1H), 7.69 (dd, 1H), 7.57 (td, 1H), 7.26-7.45 (m, 4H), 7.19 (t,1H), 7.12 (dd, 1H), 5.56 (br s, 2H). 73 δ 9.56 (d, 1H), 8.48 (s, 1H),8.08 (dd, 1H), 7.86 (d, 2H), 7.69 (dd, 1H), 7.3-7.45 (m, 3H), 7.26 (d,1H), 5.59 (br s, 2H). 74 δ 9.54 (d, 1H), 8.47 (s, 1H), 8.0-8.15 (m, 3H),7.67 (dd, 1H), 7.4 (m, 2H), 7.33 (d, 1H), 7.21 (dd, 1H), 5.59 (br s,2H). 75 δ 9.56 (d, 1H), 8.48 (s, 1H), 8.03 (dd, 1H), 7.74 (d, 2H), 7.69(dd, 1H), 7.3-7.4 (m, 3H), 6.97 (d, 2H), 5.59 (br s, 2H). 76 δ 9.56 (d,1H), 8.48 (s, 1H), 8.10 (dd, 1H), 7.97 (d, 2H), 7.6-7.75 (m, 3H), 7.41(m, 2H), 7.33 (d, 1H), 5.60 (br s, 2H). 77 δ 9.50 (d, 1H), 8.47 (s, 1H),8.08 (dd, 1H), 7.68 (dd, 1H), 7.50 (d, 1H), 7.3-7.45 (m, 5H), 5.7 (br d,1H), 5.4 (br d, 1H). 78 δ 9.52 (d, 1H), 8.48 (s, 1H), 8.11 (dd, 1H),7.68 (dd, 2H), 7.35-7.45 (m, 3H), 7.34 (d, 1H), 6.95-7.05 (m, 1H), 5.57(br s, 2H). 79 δ 9.52 (d, 1H), 8.48 (s, 1H), 8.12 (dd, 1H), 7.65-7.75(m, 2H), 7.47 (d, 1H), 7.42 (t, 2H), 7.37 (d, 1H), 5.58 (br s, 2H). 80 δ9.51 (d, 1H), 8.48 (s, 1H), 8.12 (dd, 1H), 7.69 (dd, 1H), 7.4-7.5 (m,2H), 7.33 (d, 1H), 7.27 (m, 1H), 7.02 (dd, 1H), 5.58 (br s, 2H). 82 δ9.55 (d, 1H), 8.48 (s, 1H), 8.09 (dd, 1H), 7.65-7.75 (m, 2H), 7.6 (m,1H), 7.41 (m, 2H), 7.33 (d, 1H), 7.17 (q, 1H), 5.58 (br s, 2H). 83 δ9.56 (d, 1H), 8.48 (s, 1H), 8.05 (dd, 1H), 7.70 (d, 1H), 7.28-7.40 (m,6H), 6.84 (m, 1H), 5.59 (br s, 2H), 3.84 (s, 3H). 84 δ 9.56 (d, 1H),8.48 (s, 1H), 8.03 (dd, 1H), 7.68 (m, 3H), 7.36 (m, 1H), 7.31 (d, 1H),7.23 (d, 1H), 5.58 (br s, 2H), 2.37 (s, 3H). 85 δ 9.52 (d, 1H), 8.48 (s,1H), 8.10 (dd, 1H), 7.68 (dd, 2H), 7.3-7.5 (m, 6H), 5.57 (br s, 2H). 86δ (acetone-d₆) 9.45 (d, 1H), 8.55 (d, 1H), 8.25 (m, 1H), 7.9-7.8 (m,2H), 7.75 (s, 1H), 7.6 (dd, 1H), 7.5 (m, 1H), 7.4 (d, 1H), 6.65 (d, 1H),5.72 (br s, 2H), 4.53 (m, 2H), 3.2 (m, 2H). 87 δ 9.59 (d, 1H), 8.38 (s,1H), 8.10 (dd, 1H), 7.8 (m, 3H), 7.42 (t, 1H), 7.36 (d, 1H), 7.11 (t,2H), 5.59 (br s, 2H). 88 δ 9.53 (d, 1H), 8.49 (s, 1H), 8.10 (dd, 1H),7.70 (dd, 1H), 7.26-7.45 (m, 4H), 7.10 (td, 1H), 7.00 (m, 1H), 5.58 (brs, 2H). 89 δ 9.51 (d, 1H), 8.48 (s, 1H), 8.10 (dd, 1H), 7.70 (dd, 1H),7.28-7.45 (m, 4H), 7.12 (m, 2H), 5.57 (br s, 2H). 90 δ 9.53 (d, 1H),8.47 (s, 1H), 8.13 (dd, 1H), 7.68 (d, 1H), 7.60 (s, 1H), 7.53 (s, 2H),7.43 (m, 2H), 7.35 (d, 1H) 5.60 (br d, 2H). 91 δ 9.52 (d, 1H), 8.46 (s,1H), 8.06 (dd, 1H), 7.68 (d, 1H), 7.3-7.55 (m, 5H), 7.25 (d, 1H), 5.6(br dd, 2H), 2.26 (s, 3H). 92 δ 9.54 (d, 1H), 8.48 (s, 1H), 8.1 (m, 2H),7.75 (m, 1H), 7.68 (dd, 1H), 7.4 (m, 3H), 7.37 (d, 1H), 7.15 (t, 1H),5.58 (br s, 2H). 93 δ 9.55 (d, 1H), 8.48 (s, 1H), 8.25 (s, 1H), 8.14 (s,1H), 8.11 (dd, 1H), 7.66 (m, 2H), 7.4 (m, 2H), 7.34 (d, 1H), 5.59 (br s,2H). 94 δ 9.53 (d, 1H), 8.48 (s, 1H), 8.14 (t, 1H), 7.75 (t, 1H), 7.68(dd, 1H), 7.51 (d, 1H), 7.4 (m, 3H), 7.34 (d, 1H), 5.58 (br s, 2H). 95 δ9.53 (d, 1H), 8.48 (s, 1H), 8.07 (t, 1H), 7.71 (d, 1H), 7.47 (t, 1H),7.38 (m, 2H), 7.32 (d, 1H), 6.75 (m, 2H), 5.58 (br s, 2H). 96 δ 9.53 (d,1H), 8.47 (s, 1H), 8.08 (dd, 1H), 7.69 (t, 1H), 7.3-7.45 (m, 4H),6.9-7.05 (m, 2H), 5.6 (br dd, 2H), 2.28 (s, 3H). 97 δ 9.52 (d, 1H), 8.77(s, 1H), 8.34 (t, 1H), 8.08 (dd, 1H), 7.98 (d, 1H), 7.78 (m, 2H), 7.4(m, 2H), 7.10 (d, 1H), 5.67 (br s, 2H), 2.55 (s, 3H). 98 δ 9.55 (dd,1H), 8.48 (d, 1H), 8.04 (ddd, 1H), 7.69 (dd, 1H), 7.40-7.34 (m, 2H),7.32 (d, 1H), 7.29-7.26 (m, 2H), 6.88 (d, 1H), 5.95 (s, 2H), 5.58 (br s,2H). 99 δ 9.52 (d, 1H), 8.48 (s, 1H), 8.10 (dd, 1H), 7.72 (dd, 1H),7.3-7.5 (m, 5H), 7.11 (td, 1H), 5.8 (br d, 1H), 5.4 (br d, 1H). 100 δ9.58 (d, 1H), 8.38 (s, 1H), 8.07 (dd, 1H), 7.8 (m, 3H), 7.3-7.45 (m,4H), 7.26 (m, 1H), 5.57 (br s, 2H). 101 δ 9.56 (d, 1H), 8.48 (s, 1H),8.07 (dd, 1H), 7.69 (d, 1H), 7.49 (d, 1H), 7.3-7.45 (m, 4H), 7.12 (dd,1H), 5.59 (br s, 2H), 3.93 (s, 3H). 102 δ 9.55 (d, 1H), 8.48 (s, 1H),8.05 (dd, 1H), 7.55-7.95 (m, 3H), 7.3-7.45 (m, 3H), 7.02 (dd, 1H), 5.58(br s, 2H), 3.91 (s, 3H). 103 δ 9.53 (d, 1H), 8.69 (s, 1H), 8.60 (d,1H), 8.07 (m, 2H), 7.80 (s, 1H), 7.66 (d, 1H), 7.4 (m, 2H), 7.25 (m,2H), 5.63 (br s, 2H). 104 δ 9.55 (d, 1H), 8.47 (s, 1H), 8.07 (dd, 1H),7.65-7.75 (m, 3H), 7.53 (d, 2H), 7.51 (d, 1H), 7.4 (m, 2H), 7.32 (d,1H), 5.58 (br s, 2H). 105 δ 9.56 (d, 1H), 8.48 (s, 1H), 8.12 (dd, 1H),8.02 (d, 2H), 7.67 (d, 2H), 7.4 (m, 3H), 7.34 (d, 1H), 5.59 (br s, 2H).106 δ 9.55 (d, 1H), 8.48 (s, 1H), 8.07 (dd, 1H), 7.78 (d, 2H), 7.69 (dd,1H), 7.4 (m, 4H), 7.32 (d, 1H), 5.59 (br s, 2H). 107 δ 9.53 (d, 1H),8.48 (s, 1H), 8.20 (s, 1H), 8.11 (m, 2H), 7.68 (dd, 1H), 7.4-7.55 (m,4H), 7.34 (d, 1H), 5.59 (br s, 2H). 108 δ 9.51 (d, 1H), 8.48 (s, 1H),8.11 (dd, 1H), 7.68 (dd, 1H), 7.4 (m, 3H), 7.34 (d, 1H), 6.76 (dd, 2H),5.58 (br s, 2H). 109 δ 9.57 (d, 1H), 8.46 (s, 1H), 7.88 (dd, 1H), 7.77(m, 2H), 7.57 (dd, 1H), 7.3 (m, 3H), 7.1 (m, 3H), 5.35 (br m, 1H), 2.00(s, 3H). 110 δ 9.46 (dd, 1H), 8.14 (ddd, 1H), 7.47 (d, 1H), 7.36 (m,1H), 4.31 (t, 2H), 1.87-1.70 (m, 2H), 1.07 (t, 3H). 111 δ 9.54 (d, 1H),8.26 (dd, 1H), 7.61 (d, 1H), 7.49 (t, 1H), 5.12 (br s, 2H). 112 δ 9.45(d, 1H), 8.14 (dd, 1H), 7.49 (d, 1H), 7.33 (t, 1H), 4.32 (t, 2H), 1.78(m, 2H), 1.07 (t, 3H). 113 δ 9.50 (d, 1H), 8.23 (dd, 1H), 7.52 (d, 1H),7.41 (t, 1H), 4.96 (m, 1H), 4.77 (m, 1H), 4.40 (m, 1H), 2.40 (m, 1H),2.25 (m, 1H). 114 δ (acetone-d₆) 9.42 (d, 1H), 8.53 (m, 1H), 8.09 (d,1H), 7.69 (t, 1H), 5.42 (br s, 2H). 115 δ 8.12 (d, 1H), 7.45 (dd, 1H),6.68 (dd, 1H), 6.48 (d, 1H), 4.6 (br s, 2H), 2.4 (m, 1H), 1.01 (d, 6H).116 δ 8.12 (d, 1H), 7.45 (dd, 1H), 6.68 (dd, 1H), 6.49 (d, 1H), 4.6 (brs, 2H), 1.6 (m, 1H), 0.92 (d, 6H). 117 δ 9.51 (d, 1H), 8.18 (dd, 1H),7.58 (d, 1H), 7.46 (t, 1H), 5.10 (br s, 2H), 2.91 (t, 2H), 2.60 (m, 2H).118 δ 9.49 (d, 1H), 8.45 (s, 1H), 8.12 (dd, 1H), 7.65 (dd, 1H), 7.4 (m,2H), 7.32 (d, 1H), 5.60 (br s, 2H). 119 δ 9.55 (d, 1H), 8.71 (s, 1H),8.47 (s, 1H), 8.30 (dd, 1H), 8.11 (dd, 1H), 7.67 (dd, 1H), 7.42 (m, 2H),7.33 (d, 1H), 5.60 (br s, 2H). 120 δ 9.56 (d, 1H), 8.92 (s, 1H), 8.47(s, 1H), 8.21 (dd, 1H), 8.11 (dd, 1H), 7.3-7.45 (m, 4H), 5.59 (br s,2H). 132 δ 8.23 (d, 1H), 7.64 (d, 2H), 7.23 (d, 2H), 4.06 (dd, 2H), 2.89(m, 1H), 1.89 (q, 2H), 1.25 (d, 6H), 1.06 (t, 3H). 133 δ 8.30 (d, 1H),7.46 (m, 1H), 7.16 (d, 1H), 6.8-6.9 (m, 2H), 4.8 (br s, 2H). 134 δ 8.32(d, 1H), 7.72 (d, 2H), 7.38 (dd, 2H), 7.23 (dd, 1H), 7.13 (d, 1H), 4.81(q, 2H). 135 δ 8.32 (d, 1H), 7.73 (d, 1H), 7.69 (s, 1H), 7.37 (t, 1H),7.15 (d, 1H), 7.08 (d, 1H), 4.81 (q, 2H). 136 δ 8.52 (d, 1H), 8.28 (d,1H), 7.91 (dd, 1H), 7.72 (d, 2H), 7.35-7.4 (m, 3H), 7.25 (m, 1H,partially obscured by solvent peak), 7.03 (d, 1H), 5.31 (s, 2H). 137 δ(acetone-d₆) 8.61 (d, 1H), 8.20 (d, 1H), 7.98 (d, 1H), 7.89 (m, 2H),7.55 (dd, 1H), 7.47 (m, 1H), 7.03 (dd, 2H), 5.46 (s, 2H). 138 δ 8.49 (d,1H), 8.23 (d, 1H), 7.86 (dd, 1H), 7.75 (d, 1H), 7.70 (s, 1H), 7.37 (dd,2H), 7.08 (d, 1H), 7.03 (d, 1H), 5.29 (s, 2H). 139 δ 8.29 (d, 1H),7.67-7.72 (m, 3H), 7.25 (m, 1H, partially obscured by solvent peak),7.09 (d, 1H), 5.34 (s, 2H). 140 δ 8.28 (d, 1H), 7.67-7.73 (m, 3H),7.04-7.11 (m, 3H), 5.33 (s, 2H). 141 δ 8.25 (s, 1H), 7.65-7.75 (m, 3H),7.38 (dd, 1H), 7.08 (d, 1H), 5.32 (d, 1H). 142 δ 8.01 (d, 1H), 7.39 (m,1H), 6.95 (d, 1H), 6.92-6.88 (m, 2H), 4.31 (m, 2H), 1.70 (m, 2H), 0.92(t, 3H). 147 δ 8.27 (d, 1H), 7.67 (s, 1H), 7.31 (m, 3H), 7.07 (d, 1H),6.80 (m, 1H), 5.33 (s, 2H), 3.82 (s, 3H). 152 δ 8.27 (d, 1H), 7.82 (m,1H), 7.69 (s, 1H), 7.56 (m, 1H), 7.23 (m, 1H), 7.14 (d, 1H), 5.35 (s,2H). 160 δ (acetone-d₆) 8.17 (d, 1H), 7.88 (s, 1 H), 7.59 (d, 1H),7.21-7.29 (m, 2H), 6.99 (d, 1H), 6.88 (t, 1H), 5.45 (d, 2H), 3.76 (s,3H). 171 δ 9.49 (dd, 1H), 8.18 (t, 1H), 7.65-7.75 (m, 2H), 7.38-7.49 (m,2H), 4.31 (d, 2H), 1.15-1.22 (m, 1H), 0.62 (m, 4H). 209 δ (acetone-d₆)9.45 (d, 1H), 8.48 (t, 1 H), 8.13 (d, 1H), 7.63 (t, 1H), 6.98-7.08 (m,3H), 5.38 (br d, 2H), 3.87 (s, 3H). 229 δ 9.58 (d, 1H), 8.02 (t, 1 H),7.47-7.59 (m, 3H), 7.38 (t, 1H), 7.15-7.35 (m, 4H), 2.01 (d, 3H). 345 δ9.47 (dd, 1H), 8.08 (d, 1H), 7.68 (m, 1H), 7.45-7.55 (m, 3H), 7.31 (t,2H), 7.00 (d, 2H), 4.15-4.4 (m, 2H), 4.11 (q, 2H), 1.7-1.85 (m, 2H),1.31 (t, 3H), 1.07 (t, 3H). 346 δ 9.55 (dd, 1H), 8.17 (t, 1H), 7.67 (d,1H), 7.59 (d, 1H), 7.52 (dd, 1H), 7.45 (t, 1H), 6.99 (d, 1h), 5.3 (br s,1H), 4.9 (br s, 1H), 4.10 (q, 2H), 1.31 (t, 3H). 348 δ 9.49 (dd, 1H),8.11 (t, 1H), 7.48 (d, 1H), 7.34 (m, 2H), 7.13 (s, 1H), 4.32 (m, 2H),3.71 (s, 3H), 2.29 (s, 3H), 1.7-1.85 (m, 2H), 1.06 (t, 3H). 349 δ 9.49(d, 1H), 8.05 (t, 1H), 7.48 (d, 1H), 7.29 (t, 1H), 7.16 (m, 2H), 7.01(d, 1H) 4.31 (m, 2H), 2.31 (s, 3H), 2.20 (s, 3H) 1.7-1.85 (m, 2H), 1.06(t, 3H). 351 δ 9.55 (d, 1H), 8.23 (t, 1H), 7.98 (d, 2H), 7.66 (d, 2H),7.52 (d, 1H), 7.44 (t, 1H), 4.85-5.05 (m, 1H), 4.75 (m, 1H), 4.40 (m,1H), 2.2-2.6 (m, 2H). 352 δ 9.59 (dd, 1H), 8.25 (t, 1H), 7.59 (d, 1H),7.50 (t, 1H), 7.23-7.28 (m, 1H), 7.07 (td, 1H), 7.04 (m, 1H), 5.10 (brs, 2H). 369 δ 9.60 (dd, 1H), 8.26 (t, 1H), 8.16 (d, 1H), 8.12 (m, 1H),7.62 (d, 1H), 7.53 (t, 1H), 7.20 (t, 1H), 5.10 (br s, 2H). 416 δ 9.51(d, 1H), 8.50 (s, 1H), 8.08 (d, 2H), 7.75 (d, 2H), 7.66 (dd, 2H),7.3-7.45 (m, 3H), 7.2- 7.25 (m, 1H), 5.69 (s, 2H). 418 δ 9.54 (dd, 1H),8.47 (d, 1H), 8.10 (m, 1H), 7.79 (d, 1H), 7.67(dd, 1H), 7.33-7.43 (m,2H), 7.2-7.3 (m, 3H), 5.58 (br s, 2H). 425 δ 9.56 (d, 1H), 8.48 (s, 1H),8.06 (t, 1H), 7.74 (s, 1H), 7.66 (dd, 2H), 7.3-7.4 (m, 3H), 7.19 (d,1H), 5.59 (br s, 1H), 2.51 (s, 3H). 426 δ 9.62 (dd, 1H), 8.75 (t, 1H),8.26 (m, 1H), 8.20 (d, 1H), 7.63 (d, 1H), 7.53 (m, 2H), 5.3 (br s, 2H).427 δ 9.57 (dd, 1H), 8.48 (s, 1H), 8.04 (m, 1H), 7.93 (s, 1H), 7.70 (dd,2H), 7.42 (s, 2H), 7.35 (m, 3H), 5.60 (br s, 2H), 0.29 (s, 9H). 430 δ9.56 (dd, 1H), 8.76 (s, 1H), 8.04 (m, 1H), 7.93 (d, 1H), 7.7-7.8 (m,3H), 7.60 (m, 3H), 7.34 (m, mH), 5.65 (br s, 2H), 0.28 (s, 9H). 433 δ9.58 (d, 1H), 8.22 (m, 1H), 7.61 (d, 1H), 7.48 (t, 1H), 7.30 (m, 1H),6.98 (d, 1H), 6.93 (m, 1H), 5.2 (br s, 2H), 2.24 (s, 3H). 436 δ 9.58(dd, 1H), 8.38 (s, 1H), 8.11 (t, 1H), 7.80 (m, 3H), 7.42 (m, 2H), 7.36(d, 1H), 7.11 (d, 1H), 5.58 (br s, 2H). 443 δ 9.59 (dd, 1H), 8.38 (s,1H), 8.07 (t, 1H), 7.82 (s, 1H), 7.74 (d, 2H), 7.40 (t, 1H), 7.37 (d,1H), 6.98 (d, 2H), 5.58 (br s, 2H), 3.84 (s, 3H). 453 δ 9.58 (dd, 1H),8.12 (m, 1H), 7.82 (d, 1H), 7.78 (s, 1H), 7.49 (d, 1H), 7.42 (m, 2H),7.26 (m, 2H), 7.12 (d, 1H), 5.67 (br s, 2H). 459 δ 9.55 (d, 1H), 8.45(d, 1H), 8.05 (t, 1H), 7.66 (dd, 1H), 7.52 (d, 1H), 7.42 (s, 1H),7.31-7.39 (m, 4H), 6.85 (d, 1H), 5.59 (br s, 2H), 4.38 (q, 2H). 483 δ9.57 (dd, 1H), 8.15 (m, 1H), 7.74 (m, 2H), 7.59 (d, 1H), 7.40 (t, 1H),7.08(t, 2H), 5.0 (m, 1H), 4.0 (m, 1H), 2.07 (m, 1H), 1.5-1.65 (m, 4H).486 δ (acetone-d₆) 9.43 (d, 1H), 8.41 (t, 1H), 8.18 (d, 1H), 7.96 (s,1H), 7.75 (d, 1H), 7.59 (t, 1H), 7.50-7.56 (m, 1H), 7.05 (dd, 1H), 5.77(s, 2H), 3.88 (s, 3H). 501 δ 9.51 (d, 1H), 8.21 (t, 1H), 7.67 (s, 1H),7.62 (d, 1H), 7.42 (t, 1H), 6.75 (t, 2H), 5.59 (s, 2H). 511 δ(acetone-d₆) 7.87 (dd, 1H), 7.84-7.82 (m, 2H), 7.50 (d, 1H), 7.45 (d,1H), 7.25-7.21 (m, 2H), 7.10-7.05 (m, 1H), 5.58 (s, 2H), 3.64 (s, 3H),2.29 (s, 3H). 518 δ (acetone-d₆) 8.60 (d, 1H), 8.13 (s, 1 H), 8.04 (s,1H), 8.00 (d, 1H), 7.92-7.97 (m, 2H), 7.43 (d, 1H), 7.38 (t, 1H), 7.03(d, 1H), 5.42 (s, 2H). 521 δ (acetone-d₆) 9.50 (d, 1H), 8.85 (d, 1 H),8.55 (t, 1H), 8.17 (d, 1H), 7.92 (s, 1H), 7.71 (t, 1H), 7.45 (d, 1H),5.39 (br d, 2H). 547 δ (acetone-d₆) 9.41 (d, 1H), 8.35-8.43 (m, 2H),7.98-8.05 (m, 2H), 7.88-7.92 (m, 2H), 7.63 (d, 1H), 7.59 (t, 1H), 7.05(d, 1H), 5.74 (s, 2H). 564 δ 9.53 (dd, 1H), 8.14 (m, 1H), 7.73 (m, 2H),7.4-7.6 (m, 4H), 7.36 (t, 2H), 7.20 (m, 1H), 5.58 (br s, 2H), 4.32 (m,2H), 1.84 (m, 2H), 1.09 (t, 3H). 569 δ 9.48 (dd, 1H), 8.70 (s, 1H), 8.43(d, 1H), 8.22 (d, 1H), 8.17 (m, 2H), 7.78 (d, 1H), 7.52 (d, 1h), 7.37(t, 1H) 4.3 (t, 2H), 1.83 (m, 2H), 1.09 (t, 3H). 583 δ (acetone-d₆) 9.42(dd, 1H), 8.35 (t, 1H), 8.15 (d, 1H), 7.82 (d, 2H), 7.52 (t, 1H),7.25-7.31 (m, 2H), 7.13 (t, 1H), 5.34 (Br s, 1H), 4.05 (dd, 2H), 3.58(td, 2H), 2.91 (qd, 2H), 1.80 (dd, 2H). 599 δ 9.57 (dd, 1H), 8.76 (d,1H), 8.03 (m, 1H), 7.7-7.83 (m, 4H), 7.34-7.57 (m, 6H), 7.2-7.3 (m, 2H),6.98 (dd, 1H), 5.65 (br s, 2H). 600 δ (acetone-d₆) 9.41 (d, 1H), 8.45(t, 1H), 8.20 (d, 1H), 7.95-8.05 (m, 2H), 7.88 (d, 1H), 7.59- 7.65 (m,2H), 5.75 (br s, 2H). 601 δ 9.57 (dd, 1H), 9.14 (s, 1H), 8.52 (s, 1H),8.05-8.10 (m, 2H), 7.91 (s, 26H), 7.78-7.82 (m, 2H), 7.38-7.43 (d, 2H),7.11 (t, 2H), 5.67 (Br s, 2H). 606 δ 9.49 (d, 1H), 8.53 (d, 1H), 8.05(s, 2H), 7.78 (m, 2H), 7.68 (t, 1H), 7.55 (d, 1H), 7.33 (m, 1H), 7.09(t, 2H), 5.68 (br s, 2H). 612 δ 9.44 (dd, 1H), 8.65 (d, 1H), 8.57 (dd,1H), 8.03 (m, 1H), 7.62 (dt, 1H), 7.27-7.37 (m, 3H), 5.55 (br s, 2H),5.47 (s, 1H). 638 δ 9.49 (d, 0.5H), 9.47 (d, 0.5H), 8.23 (t, 1H), 7.61(d, 1H), 7.50 (m, 1H), 5.00 (m, 2H), 4.35 (q, 1H), 4.32 (q, 1H), 1.35(t, 1.5H), 1.28 (t, 1.5H) (1:1 mix of E and Z isomers). 639 δ(acetone-d₆) 8.45 (d, 1H), 8.19 (m, 1H), 8.10 (m, 1H), 8.00 (m, 2H),7.53 (m, 1H), 7.38 (m, 1H), 7.10-7.00 (m, 2H), 5.45 (s, 2H). 646 δ(acetone-d₆) 8.45 (s, 1H), 8.10 (m, 2H), 7.50 (m, 1H), 7.30 (m, 1H),7.20 (m, 1H), 7.15 (m, 1H), 6.95 (m, 1H), 6.90 (m, 1H), 5.50-5.30 (dd,2H), 3.76 (s, 3H). 647 δ (acetone-d₆) 8.10 (m, 1H), 7.70 (s, 1H), 7.55(s, 1H), 7.50 (d, 1H), 7.25 (m, 1H), 7.20 (m, 1H), 6.95 (m, 1H), 6.90(m, 1H), 5.13 (m, 2H), 3.83 (s, 3H), 3.74 (s, 3H). 648 δ (acetone-d₆)9.40 (m, 1H), 8.10 (m, 1H), 7.70 (m, 1H), 7.60 (dd, 1H), 7.45-7.35 (m,3H), 7.20 (m, 1H), 7.05 (m, 1H), 6.95 (m, 1H), 6.90 (m, 1H), 3.83 (m,3H), 3.75 (m, 3H), 1.90 (m, 3H). 656 δ 9.50 (m, 1H), 8.23 (t, 1H), 7.61(d, 1H), 7.50 (m, 1H), 5.00 (m, 2H), 4.09 (d, 2H), 2.00 (m, 1H), 0.98(d, 4H), 0.89 (d, 2H) (2:1 mix of E and Z isomers). 657 δ 9.50 (d, 1H),8.23 (t, 1H), 7.61 (d, 1H), 7.50 (t, 1H), 5.00 (m, 2H), 1.38 (s, 9H)(single isomer). 658 δ 9.50 (m, 1H), 8.23 (t, 1H), 7.61 (d, 1H), 7.50(m, 1H), 5.00 (m, 2H), 4.00 (s, 2H), 0.99 (s, 6H), 0.89 (s, 3H) (2:1 mixof E and Z isomers). 659 δ 9.50 (m, 1H), 8.23 (t, 1H), 7.61 (d, 1H),7.50 (m, 1H), 5.00 (m, 2H), 4.82 (s, 0.66H), 4.76 (s, 1.34H), 4.22 (q,0.66H), 4.20 (q, 1.34H), 1.29 (t, 1H), 1.27 (t, 2H) (2:1 mix of E and Zisomers). 700 δ 9.44 (d, 1H), 8.22 (t, 1H), 7.64 (s, 1H), 7.58 (d, 1H),7.42 (t, 1H), 5.55 (br s, 2H), 4.42 (q, 2H), 1.04 (t, 3H). 701 δ 9.44(d, 1H), 8.26 (t, 1H), 7.91 (d, 2H), 7.65 (s, 1H), 7.63 (d, 1H), 7.55(t, 1H), 7.44 (m, 3H), 5.56 (br s, 2H). 729 δ 9.49 (d, 1H), 8.23 (s,1H), 8.21 (t, 1H), 7.52 (d, 1H), 7.47 (t, 1H), 5.05 (br m, 2H), 1.38 (s,9H). 730 δ 9.53 (d, 1H), 8.42 (s, 1H), 8.21 (t, 1H), 7.53 (d, 1H), 7.46(t, 1H), 5.05 (br m, 2H), 4.22 (q, 2H), 1.32 (t, 3H). 731 δ 9.53 (d,1H), 8.44 (s, 1H), 8.21 (t, 1H), 7.53 (d, 1H), 7.49 (t, 1H), 5.05 (br m,2H), 3.93 (s, 2H), 0.98 (s, 9H). 758 δ 9.53 (d, 1H), 8.40 (s, 1H), 8.22(t, 1H), 7.54 (d, 1H), 7.50 (t, 1H), 5.05 (br m, 2H), 3.91 (s, 3H). 759δ 9.53 (d, 1H), 8.41 (s, 1H), 8.18 (t, 1H), 7.47 (m, 3H), 7.37 (m, 3H),7.30 (t, 1H), 5.24 (s, 2H), 5.05 (br m, 2H). ^(a) ¹H NMR data are in ppmdownfield from tetramethylsilane. CDCl₃ solution unless indicatedotherwise; “acetone-d₆” is CD₃C(═O)CD₃. Couplings are designated by(s)—singlet, (d)—doublet, (t)—triplet, (m)—multiplet, (dd)—doublet ofdoublets, (ddd)—doublet of doublet of doublets, (dt)—doublet oftriplets, (td)—triplet of doublets, (br)—broad. ^(b) ¹H NMR spectra ofcompounds wherein R² is CH₂CF₃ often do not show peaks corresponding tothe CH₂CF₃ protons.

The following Tests demonstrate the control efficacy of compounds ofthis invention on specific pests. “Control efficacy” representsinhibition of invertebrate pest development (including mortality) thatcauses significantly reduced feeding. The pest control protectionafforded by the compounds is not limited, however, to these species. SeeIndex Tables A-F for compound descriptions.

Biological Examples Of The Invention Test A

For evaluating control of diamondback moth (Plutella xylostella) thetest unit consisted of a small open container with a 12-14-day-oldradish plant inside. This was pre-infested with ˜50 neonate larvae thatwere dispensed into the test unit via corn cob grits using a bazookainoculator. The larvae moved onto the test plant after being dispensedinto the test unit.

Test compounds were formulated using a solution containing 10% acetone,90% water and 300 ppm X-77® Spreader Lo-Foam Formula non-ionicsurfactant containing alkylarylpolyoxyethylene, free fatty acids,glycols and isopropanol (Loveland Industries, Inc. Greeley, Colo., USA).The formulated compounds were applied in 1 mL of liquid through a SUJ2atomizer nozzle with ⅛ JJ custom body (Spraying Systems Co. Wheaton,Ill., USA) positioned 1.27 cm (0.5 inches) above the top of each testunit. Test compounds were sprayed at 250 ppm and replicated three times.After spraying of the formulated test compound, each test unit wasallowed to dry for 1 h and then a black, screened cap was placed on top.The test units were held for 6 days in a growth chamber at 25° C. and70% relative humidity. Plant feeding damage was then visually assessedbased on foliage consumed.

Of the compounds of Formula 1 tested the following provided very good toexcellent levels of control efficacy (40% or less feeding damage and/or100% mortality): 1, 2, 3, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18,19, 20, 22, 23, 24, 25, 26, 27, 28, 32, 33, 37, 39, 40, 42, 43, 44, 45,46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63,64, 65, 66, 67, 68, 70, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 95, 97, 98, 100, 101, 102, 103,104, 106, 107, 108, 109, 120, 121, 122, 123, 128, 135, 136, 137, 138,139, 140, 141, 145, 146, 147, 148, 149, 150, 152, 153, 154, 155, 156,159, 161, 162, 164, 166, 167, 168, 169, 170, 173, 178, 179, 180, 185,186, 187, 188, 189, 190, 192, 193, 196, 197, 198, 199, 200, 201, 202,203, 205, 206, 207, 208, 209, 210, 211, 212, 215, 216, 217, 218, 219,220, 221, 222, 226, 227, 229, 232, 235, 236, 237, 240, 242, 243, 245,246, 247, 248, 252, 253, 254, 255, 256, 257, 259, 261, 262, 263, 264,266, 267, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 281, 282,284, 286, 287, 288, 289, 290, 291, 293, 294, 295, 297, 298, 299, 300,301, 302, 307, 310, 311, 312, 313, 314, 319, 321, 323, 324, 327, 330,332, 339, 340, 341, 342, 343, 347, 350, 351, 352, 353, 355, 359, 361,362, 363, 364, 366, 367, 370, 371, 372, 374, 377, 379, 380, 386, 389,391, 400, 401, 405, 406, 412, 414, 418, 421, 422, 424, 426, 427, 431,436, 438, 440, 441, 446, 459, 460, 461, 463, 469, 470, 471, 472, 473,474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487,488, 489, 490, 491, 492, 493, 494, 495, 496, 498, 499, 500, 501, 502,503, 511, 515, 524, 525, 527, 528, 529, 530, 531, 532, 534, 536, 537,539, 540, 541, 542, 544, 545, 546, 548, 549, 550, 551, 557, 562, 563,566, 567, 575, 581, 582, 589, 596, 597, 598, 600, 603, 608, 609, 613,616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 630,632, 634, 635, 636, 639, 640, 651, 652, 653, 654, 655, 663, 664, 666,667, 670, 671, 672, 679, 682, 683, 684, 685, 701, 702, 713, 715, 717,732, 733, 753, 754, 755 and 756.

Test B

For evaluating control of fall armyworm (Spodoptera frugiperda) the testunit consisted of a small open container with a 4-5-day-old maize (corn)plant inside. This was pre-infested (using a core sampler) with 10-151-day-old larvae on a piece of insect diet.

Test compounds were formulated and sprayed at 250 ppm as described forTest A. The applications were replicated three times. After spraying,the test units were maintained in a growth chamber at 25° C. and 70%relative humidity and then visually rated as described for Test A.

Of the compounds of Formula 1 tested the following provided very good toexcellent levels of control efficacy (40% or less feeding damage and/or100% mortality): 1, 3, 8, 15, 18, 22, 40, 42, 43, 44, 45, 46, 47, 48,49, 50, 51, 53, 54, 55, 56, 58, 59, 60, 62, 65, 66, 68, 70, 73, 74, 75,76, 79, 81, 83, 84, 92, 93, 95, 103, 123, 141, 145, 166, 168, 169, 173,179, 180, 185, 186, 187, 188, 189, 192, 193, 196, 200, 215, 217, 226,232, 240, 242, 245, 252, 253, 254, 255, 256, 261, 270, 272, 275, 276,277, 310, 312, 372, 418, 427, 436, 440, 451, 461, 473, 475, 476, 477,478, 479, 480, 481, 482, 484, 486, 489, 490, 491, 493, 495, 496, 498,499, 500, 501, 502, 524, 525, 530, 531, 534, 540, 541, 542, 544, 549,550, 574, 598, 609, 616, 617, 618, 619, 620, 622, 623, 624, 625, 626,627, 628, 634, 635, 636, 652, 653, 654, 655, 663, 671, 672, 682, 683,684, 685, 717, 733 and 754.

Test C

For evaluating control of green peach aphid (Myzus persicae) throughcontact and/or systemic means, the test unit consisted of a small opencontainer with a 12-15-day-old radish plant inside. This waspre-infested by placing on a leaf of the test plant 30-40 aphids on apiece of leaf excised from a culture plant (cut-leaf method). The aphidsmoved onto the test plant as the leaf piece desiccated. Afterpre-infestation, the soil of the test unit was covered with a layer ofsand.

Test compounds were formulated and sprayed at 250 ppm as described forTest A. The applications were replicated three times. After spraying ofthe formulated test compound, each test unit was allowed to dry for 1 hand then a black, screened cap was placed on top. The test units wereheld for 6 days in a growth chamber at 19-21° C. and 50-70% relativehumidity. Each test unit was then visually assessed for insectmortality.

Of the compounds of Formula 1 tested, the following resulted in at least80% mortality: 5, 10, 19, 29, 30, 31, 42, 43, 44, 49, 50, 53, 57, 59,60, 63, 64, 65, 66, 68, 71, 72, 74, 75, 77, 78, 79, 80, 82, 83, 87, 94,99, 100, 101, 102, 105, 108, 109, 111, 118, 119, 120, 123, 139, 140,151, 153, 157, 166, 171, 172, 173, 178, 180, 185, 192, 193, 196, 197,198, 200, 203, 207, 213, 214, 216, 218, 220, 224, 231, 232, 238, 256,277, 357, 365, 373, 389, 390, 394, 396, 397, 404, 407, 411, 422, 437,443, 444, 445, 463, 464, 469, 471, 472, 476, 477, 481, 482, 483, 486,491, 492, 493, 495, 496, 498, 499, 500, 501, 503, 513, 530, 531, 536,537, 540, 544, 549, 550, 575, 577, 590, 593, 597, 598, 600, 608, 617,623, 626, 627, 628, 636, 651, 653, 654, 655, 660, 700, 714 and 717.

Test D

For evaluating control of cotton melon aphid (Aphis gossypii) throughcontact and/or systemic means, the test unit consisted of a small opencontainer with a 6-7-day-old cotton plant inside. This was pre-infestedwith 30-40 insects on a piece of leaf according to the cut-leaf methoddescribed for Test C, and the soil of the test unit was covered with alayer of sand.

Test compounds were formulated and sprayed at 250 ppm as described forTest C. The applications were replicated three times. After spraying,the test units were maintained in a growth chamber and then visuallyrated as described for Test C.

Of the compounds of Formula 1 tested, the following resulted in at least80% mortality: 5, 10, 30, 31, 49, 54, 66, 75, 87, 94, 95, 166, 167, 192,193, 198, 204, 210, 213, 214, 220, 230, 231, 235, 238, 264, 277, 486,490, 540, 544, 550, 617, 619, 623, 627, 636, 653 and 654.

Test E

For evaluating control of corn planthopper (Peregrinus maidis) throughcontact and/or systemic means, the test unit consisted of a small opencontainer with a 3-4-day-old maize plant (spike) inside. White sand wasadded to the top of the soil prior to application. Test compounds wereformulated and sprayed at 250 and 50 ppm and replicated three times asdescribed for Test A. After spraying, the test units were allowed to dryfor 1 h before they were post-infested with ˜15-20 nymphs (18 to 21 dayold) by sprinkling them onto the sand with a salt shaker. A black,screened cap was placed on the top of the cylinder. The test units wereheld for 6 days in a growth chamber at 22-24° C. and 50-70% relativehumidity. Each test unit was then visually assessed for insectmortality. Of the compounds of Formula 1 tested at 250 ppm, thefollowing resulted in at least 80% mortality: 1, 2, 3, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 27, 29,30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,67, 68, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85,86, 87, 88, 89, 90, 91, 93, 94, 95, 96, 97, 98, 99, 100, 101, 103, 104,105, 106, 107, 108, 109, 111, 114, 115, 116, 118, 119, 120, 121, 122,123, 161, 162, 163, 237, 278, 279, 280, 281, 282, 283, 284, 285, 289,290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 301, 302, 304, 306,308, 309, 314, 317, 318, 319, 320, 321, 322, 323, 324, 325, 327, 329,330, 336, 340, 341, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352,353, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 368, 375,376, 377, 378, 384, 386, 389, 390, 392, 393, 394, 396, 397, 399, 400,402, 403, 404, 406, 407, 408, 409, 411, 412, 413, 414, 415, 416, 419,420, 421, 422, 423, 424, 425, 426, 428, 431, 433, 435, 436, 437, 438,441, 442, 443, 444, 445, 446, 447, 449, 450, 459, 460, 461, 462, 463,464, 465, 466, 467, 468, 469, 470, 471, 472, 474, 475, 476, 477, 479,481, 482, 483, 484, 485, 519, 556, 562, 564, 568, 570, 571, 573, 574,575, 576, 577, 579, 582, 583, 584, 586, 587, 588, 590, 591, 592, 593,594, 604, 606, 608, 611, 612, 613, 687 and 757.

Of the compounds of Formula 1 tested at 50 ppm the following providedvery good to excellent levels of control efficacy (80% or moremortality): 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19,20, 21, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 36, 38, 39, 40, 42, 43,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61,62, 63, 64, 65, 66, 67, 68, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80,81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,99, 100, 101, 102, 103, 104, 105, 107, 108, 109, 111, 118, 119, 120,121, 123, 124, 125, 134, 136, 137, 138, 139, 140, 141, 146, 147, 148,149, 150, 151, 154, 156, 157, 161, 166, 167, 168, 171, 172, 173, 180,185, 192, 193, 196, 197, 198, 199, 200, 201, 202, 203, 204, 207, 208,209, 210, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223,224, 225, 226, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239,240, 241, 243, 244, 245, 246, 247, 248, 249, 252, 254, 255, 256, 257,259, 260, 262, 264, 266, 278, 280, 284, 289, 290, 291, 292, 293, 295,297, 301, 304, 314, 318, 319, 320, 321, 323, 324, 325, 327, 330, 343,344, 345, 346, 347, 348, 349, 350, 351, 352, 357, 359, 360, 361, 362,363, 365, 376, 377, 378, 390, 392, 393, 394, 399, 400, 403, 404, 408,411, 412, 413, 414, 419, 420, 421, 422, 423, 424, 425, 426, 431, 433,435, 436, 437, 438, 441, 442, 443, 444, 446, 448, 449, 450, 456, 459,460, 461, 462, 463, 464, 466, 468, 469, 470, 471, 472, 473, 474, 475,476, 477, 481, 482, 483, 485, 486, 487, 488, 489, 490, 491, 492, 493,495, 496, 497, 498, 499, 500, 501, 502, 503, 511, 513, 514, 522, 523,524, 525, 527, 530, 531, 536, 537, 539, 540, 542, 544, 546, 547, 570,571, 573, 574, 575, 576, 577, 579, 584, 586, 587, 588, 591, 592, 593,597, 598, 599, 600, 604, 608, 613, 621, 622, 623, 625, 626, 630, 631,632, 634, 636, 637, 639, 640, 641, 643, 645, 651, 652, 663, 664, 665,666, 677, 700, 701, 702, 708, 713, 718, 751, 752, 756 and 757.

Test F

For evaluating control of potato leafhopper (Empoasca fabae) throughcontact and/or systemic means, the test unit consisted of a small opencontainer with a 5-6-day-old Soleil bean plant (primary leaves emerged)inside. White sand was added to the top of the soil and one of theprimary leaves was excised prior to application.

Test compounds were formulated and sprayed at 250 and 50 ppm, and thetests were replicated three times as described for Test A. Afterspraying, the test units were allowed to dry for 1 h before they werepost-infested with 5 potato leafhoppers (18-21-day-old adults). A black,screened cap was placed on the top of the cylinder. The test units wereheld for 6 days in a growth chamber at 24° C. and 70% relative humidity.Each test unit was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 250 ppm the following providedvery good to excellent levels of control efficacy (80% or moremortality): 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19,21, 23, 24, 25, 26, 27, 28, 29, 30, 31, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 57, 58, 59, 60,61, 62, 63, 64, 65, 66, 67, 67, 68, 70, 71, 72, 73, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96,97, 98, 99, 100, 101, 102, 104, 105, 106, 108, 109, 111, 113, 116, 117,118, 120, 120, 122, 123, 163, 163, 237, 278, 279, 280, 281, 283, 285,286, 288, 289, 291, 292, 295, 297, 302, 308, 311, 314, 315, 317, 318,324, 325, 327, 328, 330, 340, 341, 343, 344, 345, 347, 349, 352, 357,358, 359, 360, 361, 362, 363, 364, 365, 369, 375, 376, 377, 378, 381,385, 389, 390, 392, 393, 394, 396, 397, 399, 400, 403, 404, 405, 406,407, 408, 409, 410, 411, 415, 416, 417, 419, 422, 423, 424, 425, 426,431, 433, 435, 437, 438, 443, 444, 445, 446, 449, 450, 459, 460, 461,462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475,476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 515, 568, 570, 571,573, 574, 575, 581, 588, 591, 593, 604, 606, 608, 609 and 613.

Of the compounds of Formula 1 tested at 50 ppm the following providedvery good to excellent levels of control efficacy (80% or moremortality): 1, 2, 3, 5, 6, 7, 9, 10, 11, 12, 13, 14, 16, 17, 19, 21, 23,24, 25, 26, 27, 28, 29, 30, 31, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49,50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 67, 68,70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87,88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 104, 105,106, 108, 109, 111, 118, 119, 120, 123, 124, 136, 137, 138, 139, 140,141, 146, 147, 151, 153, 155, 156, 157, 160, 166, 167, 168, 171, 172,173, 178, 180, 185, 186, 189, 192, 193, 194, 196, 197, 198, 199, 200,201, 202, 203, 204, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216,217, 218, 219, 220, 222, 223, 224, 225, 226, 232, 233, 235, 236, 237,238, 240, 243, 244, 245, 246, 247, 252, 254, 255, 256, 258, 259, 260,261, 262, 264, 266, 273, 274, 277, 280, 318, 324, 327, 330, 340, 341,357, 359, 361, 362, 363, 364, 369, 374, 377, 381, 389, 390, 392, 394,396, 397, 399, 403, 404, 407, 408, 411, 416, 417, 423, 424, 431, 433,435, 437, 449, 460, 461, 462, 463, 464, 466, 467, 469, 470, 471, 472,473, 474, 475, 476, 477, 479, 480, 481, 482, 483, 486, 487, 488, 489,490, 491, 492, 493, 494, 495, 496, 497, 498, 500, 501, 502, 503, 514,515, 524, 525, 530, 531, 534, 536, 537, 539, 540, 541, 542, 544, 545,551, 570, 575, 591, 597, 598, 600, 608, 609, 617, 618, 619, 620, 621,622, 623, 624, 627, 634, 635, 641, 645, 651, 652, 653, 654, 663, 666,671, 672, 682, 702, 711, 713, 715, 717, 753, 755 and 756.

Test G

For evaluating control of the Western Flower Thrip (Franklinielllaoccidentalis) through contact and/or systemic means, the test unitconsisted of a small open container with a 5-7-day-old Soleil bean plantinside.

Test compounds were formulated and sprayed at 250 ppm and replicatedthree times as described for Test A. After spraying, the test units wereallowed to dry for 1 hour and then 22-27 adult thrips were added to theunit and then a black, screened cap was placed on top. The test unitswere held for 7 days at 25° C. and 45-55% relative humidity.

Of the compounds of Formula 1 tested the following provided very good toexcellent levels of control efficacy (30% or less plant damage and/or100% mortality): 158, 211, 212, 229, 235, 257, 258, 262, 273, 497, 528,531, 544, 549, 579, 608, 617, 635 and 682.

Test H

For evaluating control of the cat flea (Ctenocephalides felis), a testcompound was solubilized in propylene glycol/glycerol formal (60:40) andthen diluted in bovine blood to a final test rate of 30 ppm. The treatedblood was placed in a tube with the bottom of the tube covered with amembrane. Approximately 10 adult cat fleas were allowed to feed throughthe membrane on the treated blood. The adult fleas were evaluated formortality 72 h later.

Of the compounds of Formula 1 tested, the following compounds resultedin 50% or greater mortality: 1, 2, 3, 5, 6, 8, 9, 10, 12, 14, 16, 17,19, 21, 26, 29, 34, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49,50, 52, 53, 54, 55, 56, 57, 58, 59, 61, 62, 65, 66, 71, 72, 75, 76, 78,81, 82, 83, 88, 90, 92, 98, 100, 101, 103, 104, 105, 106, 107, 114, 118,119, 120, 121, 123, 124, 125, 134, 135, 136, 137, 138, 149, 150, 153,154, 155, 156, 157, 161, 166, 167, 169, 172, 179, 186, 188, 189, 190,191, 192, 193, 196, 199, 203, 204, 206, 207, 208, 210, 211, 216, 217,218, 219, 223, 224, 225, 230, 280, 281, 289, 290, 294, 295, 301, 312,314, 318, 319, 323, 324, 327, 331, 343, 346, 348, 350, 360, 361, 362,363, 364, 369, 371, 372, 373, 374, 378, 382, 383, 385, 389, 391, 393,406, 411, 420, 421, 422, 423, 431, 435, 438, 440, 461, 466, 468, 469,470, 471, 473, 475, 476, 477, 478, 479, 480, 490, 491, 492, 493, 494,495, 496, 497, 498, 500, 503, 511, 513, 521, 528, 589, 590, 592, 596,597, 599, 604 and 606.

Test I

For evaluating control of the cat flea (Ctenocephalides felis), a testcompound was solubilized in acetone:water (75:25) to a final test rateof 500 ppm. Then 20 μL of the 500 ppm solution was applied to filterpaper in the bottom of a tube. The tube was allowed to dry for 3 hours.Then approximately 10 adult fleas were added to the tube and the tubewas capped. The fleas were evaluated for mortality 48 hours later.

Of the compounds of Formula 1 tested, the following compounds resultedin 50% or greater mortality: 5, 6, 10, 12, 19, 21, 22, 23, 26, 27, 28,38, 39, 40, 41, 42, 43, 44, 45, 47, 48, 50, 54, 56, 57, 59, 61, 62, 63,65, 70, 71, 72, 75, 81, 82, 83, 102, 107, 108, 114, 115, 121, 124, 136,138, 141, 151, 154, 161, 166, 173, 186, 193, 196, 197, 203, 204, 208,211, 216, 218, 224, 229, 232, 281, 290, 291, 295, 301, 310, 321, 343,350, 353, 357, 360, 361, 364, 408, 419, 424, 437, 446, 450, 461, 464,466, 468, 470, 471, 474, 476, 483, 485, 487, 490, 491, 492, 493, 494,496, 498, 501, 507, 520, 521, 576, 597 and 599.

Test J

For evaluating control of the cat flea (Ctenocephalides felis) followingoral administration of the test compound to a mouse, a CD-1® mouse(about 30 g, male, obtained from Charles River Laboratories, Wilmington,Mass.) was orally dosed with a test compound in an amount of 10 mg/kgsolubilized in propylene glycol/glycerol formal (60:40). Two hours afteroral administration of the test compound, approximately 8 to 16 adultfleas were applied to each mouse. The fleas were then evaluated formortality 48 hours after flea application to the mouse.

Of the compounds of Formula 1 tested, the following compounds resultedin 20% or greater mortality: 2, 10, 19, 41, 42, 43, 44, 45, 46, 47, 51,56, 57, 59, 61, 63, 72, 75, 80, 81, 82, 83, 88, 92, 96, 101, 104, 105,106, 107, 111, 119, 120, 121, 123, 124, 136, 137, 140, 148, 151, 154,169, 186, 319, 461, 475, 476, 477, 493, 497, 498, 588 and 599.

What is claimed is:
 1. A compound of Formula 1,

wherein X is O; Y is O; R¹ is phenyl or a 6-membered heteroaromaticring, each optionally substituted with 1 to 3 substituents independentlyselected from the group consisting of halogen, cyano, nitro, C₁-C₄alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₂-C₄ haloalkenyl,C₂-C₄ alkylcarbonyl, C₂-C₄ haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl,C₂-C₄ alkylaminocarbonyl, C₃-C₇ dialkylaminocarbonyl, C(O)NCH₂Z²CH₂,C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₂-C₆ alkoxyalkyl, S(O)_(n)R¹²,S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆ dialkylamino, SF₅, Si(CH₃)₃, CHO,hydroxy, OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹; R² is C₂-C₆ alkyl, C₁-C₆ haloalkylor CR⁵R⁶CH₂OR²¹; or R² is C₄-C₇ cycloalkylalkyl optionally substitutedwith 1 to 4 substituents selected from the group consisting of halogen,C₁-C₂ alkyl, 1 cyclopropyl and 1CF₃; R³ and R⁴ are taken together withthe contiguous linking nitrogen and carbon atoms to form an optionallysubstituted ring R-2

Z is C(R^(8a))═C(R^(8b)), S, O or NCH₃, provided that theC(R^(8a))═C(R^(8b)) moiety is oriented so the carbon atom bonded toR^(8b) is connected as R³ in Formula 1; each R⁵ is independently H, F,Cl, cyano or C₁-C₄ alkyl; each R⁶ is independently H, F, C₁ or CH₃;R^(8a) is H; R^(8b) is H or F; each R¹² is independently C₁-C₄ alkyl orC₁-C₄ haloalkyl; each R¹³ is independently C₁-C₄ alkylamino, C₂-C₆dialkylamino or —NCH₂Z²CH₂; each R¹⁹ is independently C₁-C₄ alkyl;each R²⁰ is independently H or C₁-C₄ alkyl; each R²¹ is independently Hor C₁-C₄ alkyl; each n is independently 0, 1 or 2; and each Z² isindependently CH₂CH₂, CH₂CH₂CH₂ or CH₂OCH₂.
 2. The compound of claim 1wherein R¹ is phenyl or pyridinyl, each optionally substituted with 1 to3 substituents independently selected from the group consisting ofhalogen, cyano, nitro, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄haloalkyl, C₂-C₄ haloalkenyl, C₂-C₄ alkylcarbonyl, C₂-C₄haloalkylcarbonyl, C₂-C₄ alkoxycarbonyl, C₂-C₄ alkylaminocarbonyl, C₃-C₇dialkylaminocarbonyl, C(O)NCH₂Z²CH₂, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy,C₂-C₆ alkoxyalkyl, S(O)_(n)R¹², S(O)₂R¹³, C₁-C₄ alkylamino, C₂-C₆dialkylamino, SF₅, Si(CH₃)₃, CHO, hydroxy, OC(O)R¹⁹ and N(R²⁰)C(O)R¹⁹.3. The compound of claim 2 wherein each R⁵ is independently H or C₁-C₄alkyl.
 4. The compound of claim 3 wherein each R⁵ is independently H ormethyl.
 5. The compound of claim 4 wherein R⁶ is H.
 6. A compound ofclaim 1 that is selected from the group consisting of3-(2,4-difluorophenyl)-2-hydroxy-4-oxo-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]pyrimidiniuminner salt;3-(4-fluorophenyl)-2-hydroxy-4-oxo-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]pyrimidiniuminner salt; and2-hydroxy-4-oxo-3-phenyl-1-(2,2,2-trifluoroethyl)-4H-pyrido[1,2-a]pyrimidiniuminner salt.
 7. A composition comprising a compound of claim 1 and atleast one additional component selected from the group consisting ofsurfactants, solid diluents and liquid diluents, said compositionoptionally further comprising at least one additional biologicallyactive compound or agent.
 8. The composition of claim 7 wherein the atleast one additional biologically active compound or agent is selectedfrom the group consisting of abamectin, acephate, acequinocyl,acetamiprid, acrinathrin, amidoflumet, amitraz, avermectin,azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluoron,borate,3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide(cyantraniliprole), buprofezin, cadusafos, carbaryl, carbofuran, cartap,carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos,chlorpyrifos-methyl, chromafenozide, clofentezin, clothianidin,cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin,gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin,zeta-cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon,dieldrin, diflubenzuron, dimefluthrin, dimehypo, dimethoate,dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate,ethiprole, etofenprox, etoxazole, fenbutatin oxide, fenothiocarb,fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid,flubendiamide, flucythrinate, flufenerim, flufenoxuron, fluvalinate,tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide,hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb,insecticidal soaps, isofenphos, lufenuron, malathion, metaflumizone,metaldehyde, methamidophos, methidathion, methiodicarb, methomyl,methoprene, methoxychlor, metofluthrin, monocrotophos, methoxyfenozide,nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion,parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon,pirimicarb, profenofos, profluthrin, propargite, protrifenbute,pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl,pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine,spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat,sulprofos, sulfoxaflor, tebufenozide, tebufenpyrad, teflubenzuron,tefluthrin, terbufos, tetrachlorvinphos, tetramethrin, thiacloprid,thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin,triazamate, trichlorfon, triflumuron, Bacillus thuringiensisdelta-endotoxins, entomopathogenic bacteria, entomopathogenic virusesand entomopathogenic fungi.
 9. The composition of claim 8 wherein the atleast one additional biologically active compound or agent is selectedfrom the group consisting of abamectin, acetamiprid, acrinathrin,amitraz, avermectin, azadirachtin, bifenthrin,3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide(cyantraniliprole), buprofezin, cadusafos, carbaryl, cartap,chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin,cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin,lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin,cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin,endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole,fenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid,flubendiamide, flufenoxuron, fluvalinate, formetanate, fosthiazate,hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron,metaflumizone, methiodicarb, methomyl, methoprene, methoxyfenozide,nitenpyram, nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin,pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad,spirodiclofen, spiromesifen, spirotetramat, tebufenozide, tetramethrin,thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin,triazamate, triflumuron, Bacillus thuringiensis delta-endotoxins, allstrains of Bacillus thuringiensis and all strains of Nucleo polyhydrosisviruses.
 10. A composition for protecting an animal from an invertebrateparasitic pest comprising a parasiticidally effective amount of acompound of claim 1 and at least one carrier.
 11. A method forcontrolling an invertebrate pest comprising contacting the invertebratepest or its environment with a biologically effective amount of acompound of claim
 1. 12. A treated seed comprising a compound of claim 1in an amount of from about 0.0001 to 1% by weight of the seed beforetreatment.